Testing the Combination of Pevonedistat With Chemotherapy for Bile Duct Cancer of the Liver

Unresectable Hepatocellular Carcinoma Clinical Trial

Official title:

A Phase 2 Study of Pevonedistat in Combination With Carboplatin and Paclitaxel in Advanced Intrahepatic Cholangiocarcinoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04175912
• Other study ID #: NCI-2019-07769
• Secondary ID: NCI-2019-07769EA
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 16, 2020
• Est. completion date: October 1, 2024

Study information

• Verified date: April 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies how well pevonedistat alone or in combination with chemotherapy (paclitaxel and carboplatin) works in treating patients with bile duct cancer of the liver. Pevonedistat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This study may help the study doctors find out how well pevonedistat shrinks bile duct cancer of the liver when given alone and when in combination with paclitaxel and carboplatin.

Description:

PRIMARY OBJECTIVE: I. To determine the objective response rate of pevonedistat as a single agent and in combination with carboplatin and paclitaxel in patients with unresectable intrahepatic cholangiocarcinoma. SECONDARY OBJECTIVES: I. To evaluate the safety profile of pevonedistat alone and in combination with carboplatin and paclitaxel in patients with intrahepatic cholangiocarcinoma. II. To determine the clinical benefit rate of patients with advanced intrahepatic cholangiocarcinoma (ICC) treated with pevonedistat monotherapy and in combination with carboplatin and paclitaxel. III. To determine progression-free survival of patients treated with pevonedistat monotherapy and in combination with carboplatin and paclitaxel. IV. To determine overall survival of patients treated with pevonedistat monotherapy and in combination with carboplatin and paclitaxel. EXPLORATORY OBJECTIVES: I. To determine whether overexpression of NEDD8, NAE1, and UBC12 predict response to treatment. II. To identify the mutation profile of those cholangiocarcinomas with overexpression of the neddylation pathway. III. To bank specimens for further future investigations. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive pevonedistat intravenously (IV) over 60 minutes on days 1, 3, and 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive pevonedistat IV over 1 hour on days 1, 3, and 5, paclitaxel IV over 3 hours on day 1, and carboplatin IV over 15-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Starting cycle 5, patients may receive pevonedistat monotherapy at the discretion of treating physician. After completion of study treatment, patients are followed up at 30 days after last dose of study treatment, then every 3 months for the first year and every 6 months for years 2-3.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 52
• Est. completion date: October 1, 2024
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient must be >= 18 years of age
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patient must have a life expectancy >= 12 weeks
• Patient must have histologically confirmed intrahepatic cholangiocarcinoma or biphasic hepatocellular carcinoma and cholangiocarcinoma that is metastatic or unresectable and who have progressed on or been intolerant of one prior line of systemic gemcitabine containing chemotherapy regimen.
• NOTE: Prior immunotherapy or targeted therapies are allowed and will not be considered a line of therapy unless administered with cytotoxic chemotherapy
• Patient must have measurable disease. For patients who have received localized therapy (embolization, chemoembolization, radiofrequency ablation or radiation) are eligible if measurable disease is not within the treatment field or the treated disease has clearly progressed since last localized therapy
• Leukocytes >= 3,000/mcL (obtained within 14 days prior to randomization)
• Absolute neutrophil count >= 1,500/mcL (obtained within 14 days prior to randomization)
• Platelets >= 100,000/mcL (obtained within 14 days prior to randomization)
• Total bilirubin =< institutional upper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin =< 1.5 x ULN of the direct bilirubin (obtained within 14 days prior to randomization)
• Hemoglobin >= 9 g/dL (obtained within 14 days prior to randomization)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 14 days prior to randomization)
• Creatinine =< institutional ULN, OR glomerular filtration rate (GFR) >= 40 mL/min/1.73 m^2 (obtained within 14 days prior to randomization)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Known HIV positive patients who meet the following criteria will be considered

eligible:

• CD4 count >= 350 cells/mm^3
• Undetectable viral load
• Maintained on modern therapeutic regimens utilizing non-CYP interactive agents (i.e. excluding ritonavir)
• No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients who received prior platinum or taxane chemotherapy are eligible
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. In addition, patients with any of the known cardiopulmonary disease, defined as follows, would be ineligible

for this trial:

• Unstable angina
• Congestive heart failure (New York Heart Association [NYHA] class III or IV;);
• Myocardial infarction within 6 months prior to randomization (patients who had ischemic heart disease such as acute coronary syndrome [ACS], myocardial infarction, and/or revascularization greater than 6 months before randomization and who are without cardiac symptoms may enroll)
• Symptomatic cardiomyopathy
• Clinically symptomatic pulmonary hypertension requiring pharmacologic therapy
• Clinically significant arrhythmia, defined as:
• History of polymorphic ventricular fibrillation or torsade de pointes,
• Permanent atrial fibrillation, defined as continuous atrial fibrillation for >= 6 months,
• Persistent atrial fibrillation, defined as sustained atrial fibrillation lasting > 7 days and/or requiring cardioversion in the 4 weeks before randomization,
• Grade 3 atrial fibrillation defined as symptomatic and incompletely controlled medically, or controlled with device (e.g., pacemaker), or ablation
• Patients with paroxysmal atrial fibrillation or grade < 3 atrial fibrillation for period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen
• Patients must have the ability to understand and the willingness to sign a written informed consent document
• Participants with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible

Exclusion Criteria:

• Patients must not have had major surgery within 14 days before randomization. Patients with surgery planned during study period are ineligible
• Women must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. Patients must also not expect to conceive or father children from the time of registration, while on study treatment, and until at least 4 months after the last dose of study treatment. All females of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Women of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and continue for at least 4 months after the last dose of protocol treatment
• Male patients must not donate sperm during the course of this study or within 4 months after receiving their last dose of protocol treatment
• Female patients must not donate eggs (ova) during the course of this study or within 4 months after receiving their last dose of protocol treatment
• Patient must not have a prolonged rate corrected QT (QTc) interval >= 480 msec calculated according to institutional guideline
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e. have residual toxicities > grade 1) are ineligible with the exception of alopecia
• Patients with persistent >= grade 2 diarrhea lasting more than 3 days within 14 weeks of randomization are ineligible
• Patients with known central nervous system (CNS) involvement are ineligible
• Patients must not be receiving any other investigational agents
• Patients must not have received chemotherapy or radiotherapy within 2 weeks prior to randomization. Prior treatment with radiation therapy involving >= 25% of hematopoietically active bone marrow will be ineligible
• Patients must not have received immunotherapy within 8 weeks prior to randomization
• Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pevonedistat, carboplatin, or paclitaxel
• Patient must not be receiving any treatment with clinically significant metabolic enzyme inducers within 14 days before the first dose of the study drug as below. Clinically significant metabolic enzyme inducers are not permitted during the study. Patients must not be receiving any medications or substances that are strong inducers of CYP3A4/5 (i.e. phenytoin, rifampin, St. Johns wort) or inhibitors of breast cancer resistance protein (BCRP) (i.e. cyclosporine). Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if a new medication need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. Inhibitors of CYP3A4/5 are allowed
• Patients must not have uncontrolled intercurrent illness
• Patients must not have uncontrolled coagulopathy or bleeding disorder
• Patients must not have active, uncontrolled infection or severe infectious disease such as severe pneumonia, meningitis, or septicemia
• Patients with known moderate chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis are ineligible
• Patients must not have psychiatric illness/social situations that would limit compliance with study requirements
• Participants must not have had prior pevonedistat treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Cholangiocarcinoma
• Metastatic Cholangiocarcinoma
• Metastatic Hepatocellular Carcinoma
• Stage III Hepatocellular Carcinoma AJCC v8
• Stage III Intrahepatic Cholangiocarcinoma AJCC v8
• Stage IIIA Hepatocellular Carcinoma AJCC v8
• Stage IIIA Intrahepatic Cholangiocarcinoma AJCC v8
• Stage IIIB Hepatocellular Carcinoma AJCC v8
• Stage IIIB Intrahepatic Cholangiocarcinoma AJCC v8
• Stage IV Hepatocellular Carcinoma AJCC v8
• Stage IV Intrahepatic Cholangiocarcinoma AJCC v8
• Stage IVA Hepatocellular Carcinoma AJCC v8
• Stage IVB Hepatocellular Carcinoma AJCC v8
• Unresectable Cholangiocarcinoma
• Unresectable Hepatocellular Carcinoma
• Unresectable Intrahepatic Cholangiocarcinoma

Intervention

Drug:
• Carboplatin
Given IV
• Paclitaxel
Given IV
• Pevonedistat
Given IV

Locations

Country	Name	City	State
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	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	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	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	PCR Oncology	Arroyo Grande	California
United States	Sutter Auburn Faith Hospital	Auburn	California
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	McLaren Cancer Institute-Bay City	Bay City	Michigan
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	Overlake Medical Center	Bellevue	Washington
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Saint Charles Health System	Bend	Oregon
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
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	McFarland Clinic - Boone	Boone	Iowa
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan
United States	Bristol Regional Medical Center	Bristol	Tennessee
United States	Wellmont Medical Associates-Bristol	Bristol	Virginia
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Cambridge Medical Center	Cambridge	Minnesota
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan
United States	Caro Cancer Center	Caro	Michigan
United States	Carson Tahoe Regional Medical Center	Carson City	Nevada
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan
United States	Northwestern University	Chicago	Illinois
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	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	McLaren Cancer Institute-Clarkston	Clarkston	Michigan
United States	Newland Medical Associates-Clarkston	Clarkston	Michigan
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
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	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Mercy Hospital	Coon Rapids	Minnesota
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	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Sutter Davis Hospital	Davis	California
United States	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Porter Adventist 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	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Medical Center - 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	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
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	Fairview Southdale Hospital	Edina	Minnesota
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	University of Kansas Clinical Research Center	Fairway	Kansas
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
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	McLaren Cancer Institute-Flint	Flint	Michigan
United States	Singh and Arora Hematology Oncology PC	Flint	Michigan
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	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Vanderbilt-Ingram Cancer Center at Franklin	Franklin	Tennessee
United States	Vanderbilt-Ingram Cancer Center Cool Springs	Franklin	Tennessee
United States	Palo Alto Medical Foundation-Fremont	Fremont	California
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	UCHealth Greeley Hospital	Greeley	Colorado
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	East Carolina University	Greenville	North Carolina
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	Wayne Hospital	Greenville	Ohio
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	HaysMed University of Kansas Health System	Hays	Kansas
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	University of North Carolina-Hillsborough Campus	Hillsborough	North Carolina
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	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	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
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	Truman Medical Centers	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	University of Kansas Cancer Center-West	Kansas City	Kansas
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
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	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	Providence Regional Cancer System-Lacey	Lacey	Washington
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	Karmanos Cancer Institute at McLaren Greater Lansing	Lansing	Michigan
United States	Mid-Michigan Physicians-Lansing	Lansing	Michigan
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	McLaren Cancer Institute-Lapeer Region	Lapeer	Michigan
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	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Tenaya	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	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-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	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
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	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	Medical Center of the Rockies	Loveland	Colorado
United States	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan
United States	Michigan Breast Specialists-Macomb Township	Macomb	Michigan
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
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	Sovah Health Martinsville	Martinsville	Virginia
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Froedtert Menomonee Falls Hospital	Menomonee Falls	Wisconsin
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	UM Sylvester Comprehensive Cancer Center at Kendall	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
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	Community Medical Hospital	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Memorial Medical Center	Modesto	California
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Franciscan Health Mooresville	Mooresville	Indiana
United States	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan
United States	McLaren Cancer Institute-Central Michigan	Mount Pleasant	Michigan
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Corewell Health Lakeland Hospitals - Niles Hospital	Niles	Michigan
United States	University of Kansas Cancer Center at North Kansas City Hospital	North Kansas City	Missouri
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	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 Methodist Hospital	Omaha	Nebraska
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Hope Cancer Care of Nevada-Pahrump	Pahrump	Nevada
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Parker Adventist Hospital	Parker	Colorado
United States	McLaren Cancer Institute-Northern Michigan	Petoskey	Michigan
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida
United States	21st Century Oncology-Pontiac	Pontiac	Michigan
United States	Hope Cancer Center	Pontiac	Michigan
United States	Newland Medical Associates-Pontiac	Pontiac	Michigan
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	McLaren-Port Huron	Port Huron	Michigan
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Fairview Northland Medical Center	Princeton	Minnesota
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Saint Charles Health System-Redmond	Redmond	Oregon
United States	Corewell Health Reed City Hospital	Reed City	Michigan
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	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	Reid Health	Richmond	Indiana
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	University of Rochester	Rochester	New York
United States	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan
United States	Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
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	Salina Regional Health Center	Salina	Kansas
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Mills Health Center	San Mateo	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Sutter Pacific Medical Foundation	Santa Rosa	California
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	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
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	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Mercy Medical Center	Springfield	Massachusetts
United States	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Ascension Saint Joseph Hospital	Tawas City	Michigan
United States	Holy Name Hospital	Teaneck	New Jersey
United States	Union Hospital	Terre Haute	Indiana
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	Upper Valley Medical Center	Troy	Ohio
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
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	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	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	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	University of Michigan Health - West	Wyoming	Michigan
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
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 (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overexpression of NEDD8, NAE1, and UBC12	Will perform immunohistochemistry on formalin-fixed paraffin-embedded (FFPE) tissue determine whether overexpression of NEDD8, NAE1, and UBC12 can predict response to treatment. Biomarker quantification will be calculated as a continuous variable (mean optical density) and also as ordered categories (ex. 0, 1+, 2+, or 3+). Biomarker quantification will then be correlated with treatment response. Descriptive statistics will primarily be generated to summarize the correlative data. Statistical significance will be determined by students' t-test for normally distributed data. If data distributions are not normal, non-parametric methods will be used (Wilcoxon rank sum test).	3 years
Other	Mutation profile of cholangiocarcinomas with overexpression of the neddylation pathway		3 years
Other	Specimen banking		3 years
Primary	Objective response rate	Will assess complete or partial response by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	3 years
Secondary	Incidence of adverse events		Up to 30 days after the last dose of treatment
Secondary	Disease control rate		3 years
Secondary	Clinical benefit rate		3 years
Secondary	Progression-free survival		3 years
Secondary	Overall survival		3 years