Duloxetine to Prevent Oxaliplatin-Induced Peripheral Neuropathy in Patients With Stage II-III Colorectal Cancer

Stage III Colorectal Cancer AJCC v8 Clinical Trial

Official title:

Duloxetine to Prevent Oxaliplatin-Induced Chemotherapy-Induced Peripheral Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Phase II to Phase III Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04137107
• Other study ID #: A221805
• Secondary ID: NCI-2019-04727
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: June 17, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2024
• Source: Alliance for Clinical Trials in Oncology
• Contact: Ellen M. Lavoie Smith, PhD
• Phone: 205-996-0093
• Email: esmith3[@]uab.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II/III trial studies the best dose of duloxetine and how well it works in preventing pain, tingling, and numbness (peripheral neuropathy) caused by treatment with oxaliplatin in patients with stage II-III colorectal cancer. Duloxetine increases the amount of certain chemicals in the brain that help relieve depression and pain. Giving duloxetine in patients undergoing treatment with oxaliplatin for colorectal cancer may help prevent peripheral neuropathy.

Description:

The primary and secondary objectives of the study:

PRIMARY OBJECTIVES:

I. To determine the dosage of duloxetine hydrochloride (duloxetine) (30 mg or 60 mg daily) that appears most promising in preventing oxaliplatin-induced peripheral neuropathy (OIPN). (Phase II)

II. To demonstrate that the most promising dosage of duloxetine identified in the Phase II component is more effective than placebo at preventing OIPN sensory symptoms. (Phase III)

III. To demonstrate that the most promising dosage of duloxetine identified in the Phase II component is more effective than placebo at preventing oxaliplatin-induced chronic neuropathic pain. (Phase III)

SECONDARY OBJECTIVES:

I. To characterize toxicity in each arm, including duloxetine side effects of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. (Phase II)

II. To compare the serially measured OIPN total sensory neuropathy scores calculated from the six individual Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) questions that quantify numbness, tingling, and pain in the fingers (or hands) and toes (or feet), measured on day 1 of each cycle of oxaliplatin treatment and at 1 month post-oxaliplatin treatment between the most promising dosage of duloxetine identified in the Phase II component and placebo. (Phase III)

III. To compare the serially measured Brief Pain Inventory Short Form (BPI-SF) patient-reported on the average pain scores, measured on day 1 of each cycle of oxaliplatin treatment and at 1 month post-oxaliplatin treatment between the most promising dosage of duloxetine identified in the Phase II component and placebo.

IV. To characterize toxicity in each arm, including duloxetine side effects of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia using the CTCAE v 5.0. (Phase III)

OUTLINE:

PHASE II: Patients are randomized to 1 of 3 arms.

ARM I: Patients in Phase II receive duloxetine hydrochloride 30 mg (1 duloxetine capsule) orally (PO) once daily (QD) during week 1, duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD and placebo (1 placebo capsule) PO QD during weeks 2-16, followed by duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD during week 17 in the absence of unacceptable toxicity.

ARM II: Patients in Phase II receive duloxetine hydrochloride 30 mg (1 duloxetine capsule) orally (PO) once daily (QD) during week 1, duloxetine hydrochloride 60 mg (2 duloxetine capsules) PO QD during weeks 2-16, followed by duloxetine hydrochloride 30 mg (1 duloxetine capsule) PO QD during week 17 in the absence of unacceptable toxicity.

ARM III: Patients in Phase II receive placebo (1 placebo capsule) orally (PO) once daily (QD) during week 1, placebo (2 placebo capsules) PO QD weeks 2-16, followed by placebo (1 placebo capsule) PO QD during week 17 in the absence of unacceptable toxicity.

PHASE III: Patients are randomized to 1 of 2 arms.

ARM I: Patients in Phase III receive most promising dose of duloxetine hydrochloride from Phase II PO QD in the absence of unacceptable toxicity.

ARM II: Patients in Phase III receive placebo PO QD in the absence of unacceptable toxicity.

NOTE: Patients in all arms receive standard of care oxaliplatin during weeks 1-12.

After completion of study, patients are followed up at 30 days and at 3, 6, 12, and 18 months after last oxaliplatin treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 348
• Est. completion date: December 31, 2025
• Est. primary completion date: February 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years and older

Eligibility

• Stage II-III colorectal cancer patients scheduled to receive oxaliplatin 510 mg/m^2 (cumulative dose) over 12 weeks as a component of adjuvant leucovorin calcium (calcium folinate), 5-fluorouracil and oxaliplatin (FOLFOX) treatment, in which patients are scheduled to receive oxaliplatin 85 mg/m^2 every 2 weeks for 12 weeks (i.e., 6 cycles), or adjuvant capecitabine and oxaliplatin (CAPOX) treatment, in which patients are scheduled to receive oxaliplatin 135 mg/m^2 every 3 weeks for 12 weeks (i.e., 4 cycles)

• No prior neurotoxic chemotherapy

• No pre-existing clinical or pre-clinical peripheral neuropathy from any cause.

• No history of seizure disorder,

• No history of narrow-angle glaucoma.

• No symptoms of or history of schizophrenia, bipolar disease, suicidal thoughts and/or a major depression.

• No serious eating disorder such as bulimia or anorexia.

• No known diagnosis of ethanol (ETOH) addiction/dependence within the past 10 years.

• Concomitant medications:

• No concomitant use of other adjuvant pharmacologic interventions (e.g., gabapentin, pregabalin, venlafaxine) with known or hypothesized efficacy for peripheral neuropathy. Must be discontinued at least 7 days prior to start of protocol treatment

• No anticipated or concurrent use of any antidepressant or serotonin-altering agent known to interact with duloxetine, due to concern regarding cumulative toxicity and potential drug interactions.

• Use of a monoamine oxidase inhibitor (MAOI) or other antidepressants must be discontinued at least 14 days prior to start of protocol treatment.

• No concomitant treatment with strong CYP1A2 and CYP2D6 inhibitors.

• Chronic concomitant treatment with drugs that are extensively metabolized by CYP2D6 and that have a narrow therapeutic index, including certain antidepressants, phenothiazines, and Type 1C antiarrhythmics should be approached with caution. Concomitant administration of duloxetine and thioridazine should be avoided.

• No use of warfarin or heparin products.

• Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential, a negative pregnancy test done =< 7 days prior to registration is required

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• In order to complete the mandatory patient-completed measure, patients must be able to speak and read English

• Calculated creatinine clearance > 30 mL/min

• Aspartate aminotransferases (AST)/serum glutamic-oxaloacetic transaminase (SGOT) =< 3 x upper limit of normal (ULN)

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Peripheral Nervous System Diseases
• Stage II Colorectal Cancer AJCC v8
• Stage III Colorectal Cancer AJCC v8

Intervention

Drug:
• Oxaliplatin
Given standard of care oxaliplatin
• Duloxetine Hydrochloride
Given PO
• Duloxetine
Given PO

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies
• Placebo
Given PO

Locations

Country	Name	City	State
Guam	FHP Health Center-Guam	Tamuning
United States	Hawaii Cancer Care - Westridge	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii
United States	Straub Pearlridge Clinic	'Aiea	Hawaii
United States	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
United States	The Queen's Medical Center - West Oahu	'Ewa Beach	Hawaii
United States	Avera Cancer Institute-Aberdeen	Aberdeen	South Dakota
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	UM Upper Chesapeake Hematology and Oncology - Aberdeen	Aberdeen	Maryland
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Phoebe Putney Memorial Hospital	Albany	Georgia
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Aultman Alliance Community Hospital	Alliance	Ohio
United States	AdventHealth Altamonte	Altamonte Springs	Florida
United States	Saint Anthony's Health	Alton	Illinois
United States	UPMC Altoona	Altoona	Pennsylvania
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Mission Cancer and Blood - Ankeny	Ankeny	Iowa
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	Ascension Saint Elizabeth Hospital	Appleton	Wisconsin
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	PCR Oncology	Arroyo Grande	California
United States	AdventHealth Infusion Center Asheville	Asheville	North Carolina
United States	Hematology Oncology Associates of Central New York-Auburn	Auburn	New York
United States	Augusta Oncology Associates PC-D'Antignac	Augusta	Georgia
United States	Augusta Oncology Associates PC-Wheeler	Augusta	Georgia
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Dell Seton Medical Center at The University of Texas	Austin	Texas
United States	University of Texas at Austin	Austin	Texas
United States	Mount Sinai Comprehensive Cancer Center at Aventura	Aventura	Florida
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Kaiser Permanente-Woodlawn Medical Center	Baltimore	Maryland
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	MedStar Good Samaritan Hospital	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Louisiana Hematology Oncology Associates LLC	Baton Rouge	Louisiana
United States	LSU Health Baton Rouge-North Clinic	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Medical Center of Baton Rouge	Baton Rouge	Louisiana
United States	Ochsner High Grove	Baton Rouge	Louisiana
United States	Our Lady of The Lake	Baton Rouge	Louisiana
United States	Our Lady of the Lake Physician Group	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Beaufort Memorial Hospital	Beaufort	South Carolina
United States	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	UM Upper Chesapeake Medical Center	Bel Air	Maryland
United States	Waldo County General Hospital	Belfast	Maine
United States	Overlake Medical Center	Bellevue	Washington
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Saint Charles Health System	Bend	Oregon
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford	Biddeford	Maine
United States	Billings Clinic Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Elizabeth Boardman Hospital	Boardman	Ohio
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	McFarland Clinic - Boone	Boone	Iowa
United States	Tufts Medical Center	Boston	Massachusetts
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	United Hospital Center	Bridgeport	West Virginia
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Trinity Health Medical Center - Brighton	Brighton	Michigan
United States	Bristol Regional Medical Center	Bristol	Tennessee
United States	Wellmont Medical Associates-Bristol	Bristol	Virginia
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Ascension Southeast Wisconsin Hospital - Elmbrook Campus	Brookfield	Wisconsin
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Kaiser Permanente-Burke Medical Center	Burke	Virginia
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	Loyola Center for Health at Burr Ridge	Burr Ridge	Illinois
United States	UPMC Hillman Cancer Center at Butler Health System	Butler	Pennsylvania
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Cambridge Medical Center	Cambridge	Minnesota
United States	UPMC Camp Hill	Camp Hill	Pennsylvania
United States	Aultman Health Foundation	Canton	Ohio
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Trinity Health Medical Center - Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Carlisle Regional Cancer Center	Carlisle	Pennsylvania
United States	Mercy Cancer Center - Carmichael	Carmichael	California
United States	Mercy San Juan Medical Center	Carmichael	California
United States	Caro Cancer Center	Caro	Michigan
United States	Saint Anthony Regional Hospital	Carroll	Iowa
United States	Carson Tahoe Regional Medical Center	Carson City	Nevada
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Physicians' Clinic of Iowa PC	Cedar Rapids	Iowa
United States	AdventHealth Celebration	Celebration	Florida
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Saint Mary's Hospital	Centralia	Illinois
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Jesse Brown Veterans Affairs Medical Center	Chicago	Illinois
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Adventist Health Cancer Care Center Chico	Chico	California
United States	Ascension Calumet Hospital	Chilton	Wisconsin
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan
United States	Newland Medical Associates-Clarkston	Clarkston	Michigan
United States	Morton Plant Hospital	Clearwater	Florida
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	AdventHealth Infusion Center Haywood	Clyde	North Carolina
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Memorial Hospital North	Colorado Springs	Colorado
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Saint Francis Cancer Center	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Cookeville Regional Medical Center	Cookeville	Tennessee
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Mary Imogene Bassett Hospital	Cooperstown	New York
United States	Bay Area Hospital	Coos Bay	Oregon
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Patterson Cancer Center at UPMC Cole	Coudersport	Pennsylvania
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Heartland Oncology and Hematology LLP	Council Bluffs	Iowa
United States	Methodist Jennie Edmundson Hospital	Council Bluffs	Iowa
United States	Northshore Oncology Associates-Covington	Covington	Louisiana
United States	Ochsner Hematology Oncology North Shore - Covington (West Region)	Covington	Louisiana
United States	Greater Regional Medical Center	Creston	Iowa
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	Northwest Cancer Center - Main Campus	Crown Point	Indiana
United States	Carle at The Riverfront	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton Physician LLC - Englewood	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Kaiser Permanente-Franklin	Denver	Colorado
United States	National Jewish Health-Main Campus	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Epic Care-Dublin	Dublin	California
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Northwest Oncology LLC	Dyer	Indiana
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	University of Maryland Shore Medical Center at Easton	Easton	Maryland
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Mayo Clinic Health System-Eau Claire Clinic	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Mercy Cancer Center - Elk Grove	Elk Grove	California
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Epic Care Partners in Cancer Care	Emeryville	California
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	UPMC Hillman Cancer Center Erie	Erie	Pennsylvania
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Inova Fair Oaks Hospital	Fairfax	Virginia
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Medical Center Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Sanford South University Medical Center	Fargo	North Dakota
United States	Southpointe-Sanford Medical Center Fargo	Fargo	North Dakota
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan
United States	UPMC Cancer Center at UPMC Horizon	Farrell	Pennsylvania
United States	Saint Francis Hospital	Federal Way	Washington
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Saint Agnes Hospital/Agnesian Cancer Center	Fond Du Lac	Wisconsin
United States	Cancer Care and Hematology-Fort Collins	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Trinity Regional Medical Center	Fort Dodge	Iowa
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Beebe South Coastal Health Campus	Frankford	Delaware
United States	Ascension Saint Francis - Reiman Cancer Center	Franklin	Wisconsin
United States	Ascension Southeast Wisconsin Hospital - Franklin	Franklin	Wisconsin
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Washington Hospital	Fremont	California
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Kaiser Permanente-Gaithersburg Medical Center	Gaithersburg	Maryland
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Tidelands Georgetown Memorial Hospital	Georgetown	South Carolina
United States	Glens Falls Hospital	Glens Falls	New York
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	National Jewish Health-Western Hematology Oncology	Golden	Colorado
United States	SCL Health Cancer Centers of Colorado - Lutheran Medical Center	Golden	Colorado
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	Nebraska Cancer Specialists/Oncology Hematology West PC	Grand Island	Nebraska
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Corewell Health Grand Rapids Hospitals - Butterworth Hospital	Grand Rapids	Michigan
United States	Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Banner North Colorado Medical Center	Greeley	Colorado
United States	UCHealth Greeley Hospital	Greeley	Colorado
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Oncology Hematology Associates	Greenville	Pennsylvania
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	UPMC Hillman Cancer Center in Greenville/UPMC Horizon	Greenville	Pennsylvania
United States	Wayne Hospital	Greenville	Ohio
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan
United States	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan
United States	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	UPMC Pinnacle Harrisburg	Harrisburg	Pennsylvania
United States	Hartford Hospital	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	HaysMed	Hays	Kansas
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Lehigh Valley Hospital-Hazleton	Hazleton	Pennsylvania
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Horizon Ridge	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	GenesisCare USA - Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	Las Vegas Urology - Green Valley	Henderson	Nevada
United States	Las Vegas Urology - Pebble	Henderson	Nevada
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Urology Specialists of Nevada - Green Valley	Henderson	Nevada
United States	AdventHealth Hendersonville	Hendersonville	North Carolina
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	Northwest Cancer Center - Hobart	Hobart	Indiana
United States	Saint Mary Medical Center	Hobart	Indiana
United States	Loyola Medicine Homer Glen	Homer Glen	Illinois
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Hawaii Diagnostic Radiology Services LLC	Honolulu	Hawaii
United States	Island Urology	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Terrebonne General Medical Center	Houma	Louisiana
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Michael E DeBakey VA Medical Center	Houston	Texas
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	IRMC Cancer Center	Indiana	Pennsylvania
United States	Saint Catherine Hospital	Indianapolis	Indiana
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	MU Health Care Goldschmidt Cancer Center	Jefferson City	Missouri
United States	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania
United States	Duly Health and Care Joliet	Joliet	Illinois
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Straub Medical Center - Kahului Clinic	Kahului	Hawaii
United States	Castle Medical Center	Kailua	Hawaii
United States	Ascension Borgess Cancer Center	Kalamazoo	Michigan
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	University Health Truman Medical Center	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Ochsner Medical Center Kenner	Kenner	Louisiana
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Kaiser Permanente - Kensington Medical Center	Kensington	Maryland
United States	First Dayton Cancer Care	Kettering	Ohio
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Kingman Regional Medical Center	Kingman	Arizona
United States	Ballad Health Cancer Care - Kingsport	Kingsport	Tennessee
United States	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	AdventHealth Kissimmee	Kissimmee	Florida
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Marshfield Medical Center - Ladysmith	Ladysmith	Wisconsin
United States	Kaiser Permanente-Rock Creek	Lafayette	Colorado
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	City of Hope Antelope Valley	Lancaster	California
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	Kaiser Permanente - Largo Medical Center	Largo	Maryland
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Ann M Wierman MD LTD	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Town Center	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	Desert West Surgery	Las Vegas	Nevada
United States	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada
United States	Hope Cancer Care of Nevada	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Las Vegas Prostate Cancer Center	Las Vegas	Nevada
United States	Las Vegas Urology - Cathedral Rock	Las Vegas	Nevada
United States	Las Vegas Urology - Pecos	Las Vegas	Nevada
United States	Las Vegas Urology - Smoke Ranch	Las Vegas	Nevada
United States	Las Vegas Urology - Sunset	Las Vegas	Nevada
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at MountainView	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	University Cancer Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Central	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Northwest	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Southwest	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Beebe Medical Center	Lewes	Delaware
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Saint Joseph Hospital	Lexington	Kentucky
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Cancer Partners of Nebraska	Lincoln	Nebraska
United States	Cancer Partners of Nebraska - Pine Lake	Lincoln	Nebraska
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	CARTI Cancer Center	Little Rock	Arkansas
United States	John L McClellan Memorial Veterans Hospital	Little Rock	Arkansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Hope Cancer Clinic	Livonia	Michigan
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Saint Joseph London	London	Kentucky
United States	Kaiser Permanente-Lone Tree	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Jewish Hospital	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Banner McKee Medical Center	Loveland	Colorado
United States	Medical Center of the Rockies	Loveland	Colorado
United States	Kaiser Permanente Lutherville - Timonium Medical Center	Lutherville	Maryland
United States	Centra Alan B Pearson Regional Cancer Center	Lynchburg	Virginia
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Michigan Breast Specialists-Macomb Township	Macomb	Michigan
United States	Cancer Center of Kansas-Manhattan	Manhattan	Kansas
United States	Mayo Clinic Health Systems-Mankato	Mankato	Minnesota
United States	Cleveland Clinic Cancer Center Mansfield	Mansfield	Ohio
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Contra Costa Regional Medical Center	Martinez	California
United States	WVUH-Berkely Medical Center	Martinsburg	West Virginia
United States	Sovah Health Martinsville	Martinsville	Virginia
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania
United States	Kaiser Permanente Tysons Corner Medical Center	McLean	Virginia
United States	Cancer Center of Kansas - McPherson	McPherson	Kansas
United States	UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion	Mechanicsburg	Pennsylvania
United States	Bon Secours Memorial Regional Medical Center	Mechanicsville	Virginia
United States	Marjorie Weinberg Cancer Center at Loyola-Gottlieb	Melrose Park	Illinois
United States	Froedtert Menomonee Falls Hospital	Menomonee Falls	Wisconsin
United States	Ascension Columbia Saint Mary's Hospital Ozaukee	Mequon	Wisconsin
United States	Mercy Cancer Center	Merced	California
United States	Midstate Medical Center	Meriden	Connecticut
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Bon Secours Saint Francis Medical Center	Midlothian	Virginia
United States	Bon Secours Westchester Emergency Center	Midlothian	Virginia
United States	Ascension Columbia Saint Mary's Hospital - Milwaukee	Milwaukee	Wisconsin
United States	Ascension Saint Francis Hospital	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Center	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Trinity Medical Center	Moline	Illinois
United States	UPMC Hillman Cancer Center - Monroeville	Monroeville	Pennsylvania
United States	Monticello Cancer Center	Monticello	Minnesota
United States	UPMC Hillman Cancer Center in Coraopolis	Moon	Pennsylvania
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	UPMC Hillman Cancer Center - Part of Frick Hospital	Mount Pleasant	Pennsylvania
United States	Saint Joseph Mount Sterling	Mount Sterling	Kentucky
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Skagit Regional Health Cancer Care Center	Mount Vernon	Washington
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Inspira Medical Center Mullica Hill	Mullica Hill	New Jersey
United States	The Community Hospital	Munster	Indiana
United States	Women's Diagnostic Center - Munster	Munster	Indiana
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Arnold Palmer Cancer Center Medical Oncology Norwin	N. Huntingdon	Pennsylvania
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Providence Queen of The Valley	Napa	California
United States	UPMC Cancer Center-Natrona Heights	Natrona Heights	Pennsylvania
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	UPMC Hillman Cancer Center - New Castle	New Castle	Pennsylvania
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Corewell Health Lakeland Hospitals - Niles Hospital	Niles	Michigan
United States	Bon Secours DePaul Medical Center	Norfolk	Virginia
United States	Southwest VA Regional Cancer Center	Norton	Virginia
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Nyack Hospital	Nyack	New York
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	HSHS Saint Elizabeth's Hospital	O'Fallon	Illinois
United States	Drexel Town Square Health Center	Oak Creek	Wisconsin
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	Integris Cancer Institute of Oklahoma	Oklahoma City	Oklahoma
United States	Integris Southwest Medical Center	Oklahoma City	Oklahoma
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Nebraska Cancer Specialists/Oncology Hematology West PC - MECC	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Oncology Associates PC	Omaha	Nebraska
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	AdventHealth East Orlando	Orlando	Florida
United States	AdventHealth Medical Group Urology at Orlando	Orlando	Florida
United States	AdventHealth Orlando	Orlando	Florida
United States	Lake Regional Hospital	Osage Beach	Missouri
United States	Ascension Mercy Hospital	Oshkosh	Wisconsin
United States	ThedaCare Cancer Care - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Hope Cancer Care of Nevada-Pahrump	Pahrump	Nevada
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Parker Adventist Hospital	Parker	Colorado
United States	Camden Clark Medical Center	Parkersburg	West Virginia
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
United States	Freeman Physician Group of Pittsburg	Pittsburg	Kansas
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC-Mercy Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania
United States	UPMC-Saint Clair Hospital Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC-Saint Margaret	Pittsburgh	Pennsylvania
United States	South Florida Baptist Hospital	Plant City	Florida
United States	Beth Israel Deaconess Hospital-Plymouth	Plymouth	Massachusetts
United States	Hope Cancer Center	Pontiac	Michigan
United States	Michigan Healthcare Professionals Pontiac	Pontiac	Michigan
United States	Newland Medical Associates-Pontiac	Pontiac	Michigan
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Bon Secours Maryview Medical Center	Portsmouth	Virginia
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Fairview Northland Medical Center	Princeton	Minnesota
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Princeton Community Hospital	Princeton	West Virginia
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Ascension All Saints Hospital	Racine	Wisconsin
United States	Eisenhower Medical Center	Rancho Mirage	California
United States	Saint Charles Health System-Redmond	Redmond	Oregon
United States	Corewell Health Reed City Hospital	Reed City	Michigan
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Radiation Oncology Associates	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Valley Medical Center	Renton	Washington
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Bon Secours Cancer Institute at Reynolds Crossing	Richmond	Virginia
United States	Bon Secours Richmond Community Hospital	Richmond	Virginia
United States	Bon Secours Saint Mary's Hospital	Richmond	Virginia
United States	Reid Health	Richmond	Indiana
United States	VCU Massey Cancer Center at Stony Point	Richmond	Virginia
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	West Suburban Medical Center	River Forest	Illinois
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan
United States	OSF Saint Anthony Medical Center	Rockford	Illinois
United States	Mercy Cancer Center - Rocklin	Rocklin	California
United States	Penobscot Bay Medical Center	Rockport	Maine
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Cancer Care Associates PC	Royal Oak	Michigan
United States	Comprehensive Medical Center PLLC	Royal Oak	Michigan
United States	Hematology Oncology Consultants PC	Royal Oak	Michigan
United States	Oakland Colon Rectal Associates	Royal Oak	Michigan
United States	Oakland Medical Group	Royal Oak	Michigan
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Mercy Cancer Center - Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Mease Countryside Hospital	Safety Harbor	Florida
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Covenant HealthCare Mackinaw	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Corewell Health Lakeland Hospitals - Saint Joseph Hospital	Saint Joseph	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Siteman Cancer Center at Christian Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Saint Anthony's Hospital Cancer Care Center	Saint Petersburg	Florida
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Salina Regional Health Center	Salina	Kansas
United States	Zuckerberg San Francisco General Hospital	San Francisco	California
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	North Coast Cancer Care	Sandusky	Ohio
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford	Sanford	Maine
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Providence Medical Foundation - Santa Rosa	Santa Rosa	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Community Medical Center	Scranton	Pennsylvania
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-Cherry Hill	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Memorial Hospital East	Shiloh	Illinois
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Saint Michael Cancer Center	Silverdale	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	VCU Community Memorial Health Center	South Hill	Virginia
United States	City of Hope South Pasadena	South Pasadena	California
United States	Maine Medical Partners - South Portland	South Portland	Maine
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Mercy Medical Center	Springfield	Massachusetts
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Stamford Hospital/Bennett Cancer Center	Stamford	Connecticut
United States	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Premier Hematology Oncology Care	Sterling Heights	Michigan
United States	Trinity's Tony Teramana Cancer Center	Steubenville	Ohio
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Bon Secours Health Center at Harbour View	Suffolk	Virginia
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	Southwest Illinois Health Services LLP	Swansea	Illinois
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Hematology Oncology Associates of Central New York-Onondaga Hill	Syracuse	New York
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	Holy Name Hospital	Teaneck	New Jersey
United States	Sanford Thief River Falls Medical Center	Thief River Falls	Minnesota
United States	National Jewish Health-Northern Hematology Oncology	Thornton	Colorado
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	Hematology Oncology Consultants PC-Troy	Troy	Michigan
United States	Michigan Institute of Urology-Town Center	Troy	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	UPMC Cancer Center-Uniontown	Uniontown	Pennsylvania
United States	City of Hope Upland	Upland	California
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Northwest Cancer Center - Valparaiso	Valparaiso	Indiana
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Epic Care Cyberknife Center	Walnut Creek	California
United States	Advanced Breast Care Center PLLC	Warren	Michigan
United States	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan
United States	Macomb Hematology Oncology PC	Warren	Michigan
United States	Michigan Breast Specialists-Warren	Warren	Michigan
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Saint Joseph Warren Hospital	Warren	Ohio
United States	South Pointe Hospital	Warrensville Heights	Ohio
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	Kaiser Permanente-Capitol Hill Medical Center	Washington	District of Columbia
United States	Marion L Shepard Cancer Center - ECU Health Beaufort Hospital	Washington	North Carolina
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Mercy Hospital Washington	Washington	Missouri
United States	UPMC Cancer Center-Washington	Washington	Pennsylvania
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Ascension Medical Group Southeast Wisconsin - Mayfair Road	Wauwatosa	Wisconsin
United States	AdventHealth Infusion Center Weaverville	Weaverville	North Carolina
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Froedtert West Bend Hospital/Kraemer Cancer Center	West Bend	Wisconsin
United States	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	UPMC West Mifflin-Cancer Center Jefferson	West Mifflin	Pennsylvania
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Divine Providence Hospital	Williamsport	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Shenandoah Oncology PC	Winchester	Virginia
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	AdventHealth Winter Park	Winter Park	Florida
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Kaiser Permanente-Caton Hill Medical Center	Woodbridge	Virginia
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Woodland Memorial Hospital	Woodland	California
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	Sanford Cancer Center Worthington	Worthington	Minnesota
United States	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	University of Michigan Health - West	Wyoming	Michigan
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	Avera Cancer Institute at Yankton	Yankton	South Dakota
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	UPMC Memorial	York	Pennsylvania
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Saint Elizabeth Youngstown Hospital	Youngstown	Ohio
United States	Huron Gastroenterology PC	Ypsilanti	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Guam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevention of sensory oxaliplatin-induced peripheral neuropathy (OIPN) response (Phase II)	Will be measured using 6 individual Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) questions that quantify numbness, tingling, and pain in the fingers (or hands) and toes (or feet). For each of the 6 individual questions, patients are asked to select 1 of 4 choices regarding how each of the sensory symptoms had affected them during the preceding week: 1 = Not at all, 2 = A little, 3 = Quite a bit, and 4 = Very much. Response will be defined as a patient reporting a highest score of = 2 at any time during oxaliplatin exposure, including 1 month post-oxaliplatin treatment without discontinuing the study due to sensory oxaliplatin-induced peripheral neuropathy. The proportion of responders within each arm will be estimated by the number of responders divided by the total number of evaluable patients. Two-sided 90% exact confidence intervals for the true response proportion will be calculated according to the approach of Clopper and Pearson.	Up to 1 month post-oxaliplatin treatment
Primary	Prevention of sensory oxaliplatin-induced peripheral neuropathy (OIPN) response (Phase III)	Will be measured using 6 individual Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) questions that quantify numbness, tingling, and pain in the distal extremities. For each of the 6 questions, patients are asked to select 1 of 4 choices regarding how each of the sensory symptoms had affected them during the preceding week: 1=Not at all, 2=A little, 3=Quite a bit, and 4=Very much. Response will be defined as a patient reporting a highest score of = 2 at any time during oxaliplatin exposure, including 1 month post-oxaliplatin treatment without discontinuing the study due to sensory OIPN. The analysis population is defined as all randomized patients who received at least 1 dose of oxaliplatin and have completed the 6 QLQCIPN20 sensory symptom items on at least 1 occasion during oxaliplatin treatment, including 1 month post-oxaliplatin treatment. The Fisher exact test will be used for a between-arm comparison of the proportion of responders.	Up to 1 month post-oxaliplatin treatment
Primary	Chronic neuropathic pain response (Phase III)	Response will be defined as a 7-day average of chronic neuropathic pain (on the average) = 3 on a 0 (no pain) to 10 (pain as bad as you can imagine) scale 1 month after oxaliplatin treatment, which is obtained from the 7-day chronic neuropathy pain diary. The analysis population is defined as all randomized patients who received at least 1 dose of oxaliplatin and have completed the 7-day chronic neuropathy pain diary on at least 3 of the 7 days 1 month after the last oxaliplatin dose. The Fisher exact test will be used for a between-arm comparison of the proportion of responders.	Up to 1 month after oxaliplatin treatment
Secondary	Incidence of adverse events, including duloxetine side effects of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia (Phase II)	The constellation of adverse events as scored using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 will be summarized within arms by reporting the number and percentages of patients. The proportion of each of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia using NCI CTCAE v 5.0 will be estimated within arms with the exact 90% confidence interval.	Up to 1 month post-oxaliplatin treatment
Secondary	Serially measured total sensory neuropathy scores (Phase III)	The sequence of the total sensory neuropathy scores for each patient will be measured from the Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) questionnaire, measured on day 1 of each cycle of oxaliplatin treatment and at 1 month post-oxaliplatin treatment. The corresponding area under the curve will be computed for each arm based on estimated parameters from a repeated-measures (means) mixed model and compared. The analysis population is defined as all randomized patients who received at least 1 dose of oxaliplatin and have a total sensory neuropathy score on at least 1 occasion during oxaliplatin treatment, including 1 month post-oxaliplatin treatment.	Up to 1 month post-oxaliplatin treatment
Secondary	Serially measured patient reported on the average pain scores (Phase III)	For each patient, the total sensory neuropathy score is calculated by summing the 6 individual Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) questions that quantify numbness, tingling, and pain in the fingers (or hands) and toes (or feet) and ranges from 1 to 24, where higher numbers indicate more severe symptoms. The sequence of the total sensory neuropathy scores for each patient will be measured on day 1 of each cycle of oxaliplatin treatment and at 1 month post-oxalipatin treatment. The corresponding area under the curve will be computed for each arm based on estimated parameters from a repeated-measures (means) mixed model and compared. The analysis population is defined as all randomized patients who received at least 1 dose of oxaliplatin and have a total sensory neuropathy score on at least 1 occasion during oxaliplatin treatment, including 1 month post-oxaliplatin treatment.	Up to 1 month post-oxaliplatin treatment
Secondary	Incidence of adverse events, including duloxetine side effects of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia (Phase III)	The constellation of adverse events as scored using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 will be summarized within arms by reporting the number and percentages of patients. The proportion of each of nausea, dry mouth, dizziness, somnolence, fatigue, and insomnia using NCI CTCAE v5.0 will be estimated within arms with the exact 95% confidence interval.	Up to 1 month post-oxaliplatin treatment