Pembrolizumab in Treating Patients With Desmoplastic Melanoma That Can or Cannot Be Removed by Surgery

Desmoplastic Melanoma Clinical Trial

Official title:

A Phase II and Pilot Trial of PD-1 Blockade With Pembrolizumab (MK-3475) in Patients With Resectable or Unresectable Desmoplastic Melanoma (DM)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02775851
• Other study ID #: NCI-2016-00666
• Secondary ID: NCI-2016-00666S1
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 6, 2017
• Est. completion date: January 4, 2025

Study information

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

Clinical Trial Summary

This pilot phase II trial studies how well pembrolizumab works in treating patients with desmoplastic melanoma (DM) that can be removed by surgery (resectable) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Description:

PRIMARY OBJECTIVES:

I. To evaluate the pathologic complete response rate (pCR) in patients with resectable desmoplastic melanoma treated with neoadjuvant pembrolizumab (MK-3475). (Cohort A) II. To evaluate the complete response rate (confirmed and unconfirmed) in patients with unresectable desmoplastic melanoma treated with pembrolizumab (MK-3475). (Cohort B)

SECONDARY OBJECTIVES:

I. To estimate the 9 week response rate (RR) (unconfirmed complete and partial responses) among patients with measurable disease. (Cohort A) II. To estimate the median overall survival (OS). (Cohort A) III. To evaluate safety and tolerability of pembrolizumab (MK-3475) in the neoadjuvant setting. (Cohort A) IV. To estimate the median progression-free survival (PFS). (Cohort B) V. To estimate the median overall survival (OS). (Cohort B) VI. To evaluate safety and tolerability of pembrolizumab (MK-3475) in this setting. (Cohort B)

OTHER OBJECTIVES:

I. To evaluate the hypothesis that higher mutational load in the patient derived baseline tumor biopsy samples is associated with higher pathologic complete response (pCR).

II. To evaluate T cell infiltration into the tumors and circulating tumor deoxyribonucleic acid (DNA) profile from blood samples in DM patients and correlate with response to programmed cell death protein 1 (PD-1) blockade.

III. To evaluate the clonality of tumor infiltrating T cells in DM patients and correlate with response to PD-1 blockade.

IV. To evaluate adaptive immune resistant mechanism in DM tumors.

OUTLINE: Patients are enrolled to 1 of 2 cohorts.

COHORT A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles. Patients with potentially resectable disease undergo surgery. Patients with tumor progression and unresectable disease may receive one additional cycle of pembrolizumab.

COHORT B: Patients with unresectable disease receive pembrolizumab IV over 30 minutes on day

1. Treatment repeats every 21 days for up to 34 cycles in the absence of disease progression or toxicity.

Patients undergo computed tomography (CT) scan and may undergo position emission tomography (PET) and magnetic resonance imaging (MRI) throughout the study. Patients also undergo blood sample collection at screening and tumor biopsy throughout the study.

After completion of study treatment, patients are followed up at 6 weeks after the last dose, then every 12 weeks to the end of the first year, then every 6 months to the end of the fifth year after registration. After progression, patients are followed every 6 months for up to 2 years from the date of registration, then annually thereafter until 5 years from registration.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 57
• Est. completion date: January 4, 2025
• Est. primary completion date: April 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• COHORT A: Patients must have histologically or cytologically confirmed primary desmoplastic melanoma that is deemed resectable; the decision to perform surgery on patients must be based on good clinical judgment; eligible patients for surgical resection must have disease that, in the judgment of the surgeon, is deemed completely resectable resulting in free surgical margins; patients must have residual disease after initial biopsy which can be measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; residual disease can either be confirmed with fine-needle aspiration (FNA) or if measurable disease is present, no FNA needs to be obtained OR

• COHORT B: Patients must have histologically or cytologically confirmed primary desmoplastic melanoma that is unresectable; patients in Cohort B must have measurable disease per RECIST 1.1

• Contrast-enhanced computed tomography (CT) scans of the chest, abdomen and pelvis are required; a whole body positron emission tomography (PET)/CT scan with diagnostic quality images and intravenous iodinated contrast may be used in lieu of a contrast enhanced CT of the chest, abdomen and pelvis; imaging of the head and neck is required only if the patient has a head/neck primary; contrast may be omitted if the treating investigator believes that exposure to contrast poses an excessive risk to the patient; if skin lesions are being followed as measurable disease, photograph with a ruler included and physician measurements, must be kept in the patient's chart as source documentation; all measurable lesions must be assessed within 28 days prior to registration; tests to assess non-measurable disease must be performed within 42 days prior to registration; all disease must be assessed and documented on the baseline tumor assessment form (RECIST 1.1)

• Patients must not have known brain metastases unless brain metastases have been treated and patient is asymptomatic with no residual neurological dysfunction and has not received enzyme-reducing anti-epileptic drugs or corticosteroids for at least 14 days prior to registration

• Patients must not have received prior systemic treatment for this melanoma

• Patients must not be planning to receive concomitant other biologic therapy, hormonal therapy, other chemotherapy, anti-cancer surgery or other anti-cancer therapy while on this protocol

• Patients must not have received radiation therapy, non-cytotoxic agents or investigational agents or systemic corticosteroids within 14 days prior to registration

• Patients may have received prior surgery; all adverse events associated with prior surgery must have resolved to =< grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] 4.0) prior to registration

• Patients must be >= 18 years of age

• Absolute neutrophil count (ANC) >= 1,500/mcl (obtained within 28 days prior to registration)

• Platelets >= 50,000/mcl (obtained within 28 days prior to registration)

• Hemoglobin >= 8 g/dL (obtained within 28 days prior to registration)

• Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (or =< 3.0 x IULN with Gilbert's syndrome) (obtained within 28 days prior to registration)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x IULN (or < 5 x IULN for patients with known liver metastases) (obtained within 28 days prior to registration)

• Patients must have lactate dehydrogenase (LDH) performed within 28 days prior to registration

• Patients must have Zubrod performance status =< 2

• Patients must not have history of (non-infectious) pneumonitis that required steroids or current pneumonitis

• Patients must not have an active infection requiring systemic therapy

• Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

• Patients must not have received live vaccines within 42 days prior to registration; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, shingles, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine; seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed

• Patients known to be human immunodeficiency virus (HIV) positive prior to registration are eligible if they meet the following criteria within 30 days prior to registration: stable and adequate CD4 counts (>= 350 mm^3), and serum HIV viral load of < 25,000 IU/ml; patients must be on a stable anti-viral therapy

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated in situ cancer, adequately treated stage I or II cancer (including multiple primary melanomas) from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years

• Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days prior to registration; women/men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study through 120 days after the last dose of study medication; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures; patients must not be pregnant or nursing due to unknown teratogenic side effects

• Patients must have specimens available and institutions must be planning to submit for centralized pathology review and for integrated translational medicine objectives

• Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

• As a part of the Oncology Patient Enrollment Network (OPEN) registration process, the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

Related Conditions & MeSH terms

• Desmoplastic Melanoma
• Melanoma

Intervention

Procedure:
• Biopsy
Undergo tumor biopsy
• Biospecimen Collection
Undergo blood sample collection
• Computed Tomography
Undergo CT scan
• Magnetic Resonance Elastography
Undergo MRI

Biological:
• Pembrolizumab
Given IV

Procedure:
• Positron Emission Tomography
Undergo PET scan
• Therapeutic Conventional Surgery
Undergo surgical resection

Locations

Country	Name	City	State
United States	Saint Anthony's Health	Alton	Illinois
United States	American Fork Hospital / Huntsman Intermountain Cancer Center	American Fork	Utah
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	MultiCare Auburn Medical Center	Auburn	Washington
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	The Medical Center of Aurora	Aurora	Colorado
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	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Saint Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Boulder Community Foothills Hospital	Boulder	Colorado
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
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	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Roswell Park Cancer Institute	Buffalo	New York
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 James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Cambridge Medical Center	Cambridge	Minnesota
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Rocky Mountain Cancer Centers - Centennial	Centennial	Colorado
United States	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming
United States	Northwestern University	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Coffeyville Regional Medical Center	Coffeyville	Kansas
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
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	Carle at The Riverfront	Danville	Illinois
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Delaware Radiation Oncology	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Cancer Center of Colorado at Sloan's Lake	Denver	Colorado
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	National Jewish Health-Main Campus	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	The Women's Imaging Center	Denver	Colorado
United States	Western Surgical Care	Denver	Colorado
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Dublin Methodist Hospital	Dublin	Ohio
United States	Epic Care-Dublin	Dublin	California
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Carle Physician Group-Effingham	Effingham	Illinois
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	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Deaconess Clinic Downtown	Evansville	Indiana
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	University of Kansas Clinical Research Center	Fairway	Kansas
United States	Farmington Health Center	Farmington	Utah
United States	Saint Francis Hospital	Federal Way	Washington
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Unity Hospital	Fridley	Minnesota
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington
United States	National Jewish Health-Western Hematology Oncology	Golden	Colorado
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Nebraska Cancer Specialists/Oncology Hematology West PC	Grand Island	Nebraska
United States	Grand Valley Oncology	Grand Junction	Colorado
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
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	Mount Carmel Grove City Hospital	Grove City	Ohio
United States	Hartford Hospital	Hartford	Connecticut
United States	HaysMed	Hays	Kansas
United States	Saint Peter's Community Hospital	Helena	Montana
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Allegiance Health	Jackson	Michigan
United States	Onslow Memorial Hospital	Jacksonville	North Carolina
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Research Medical Center	Kansas City	Missouri
United States	The University of Kansas Cancer Center-South	Kansas City	Missouri
United States	University Health Truman Medical Center	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	Good Samaritan Medical Center	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	Fairfield Medical Center	Lancaster	Ohio
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	Kansas Institute of Medicine Cancer and Blood Center	Lenexa	Kansas
United States	Minimally Invasive Surgery Hospital	Lenexa	Kansas
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Saint Rita's Medical Center	Lima	Ohio
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Logan Regional Hospital	Logan	Utah
United States	Saint Joseph London	London	Kentucky
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	Los Angeles General Medical Center	Los Angeles	California
United States	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
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	OhioHealth Mansfield Hospital	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	Marietta Memorial Hospital	Marietta	Ohio
United States	OhioHealth Marion General Hospital	Marion	Ohio
United States	Contra Costa Regional Medical Center	Martinez	California
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Mount Sinai Medical Center	Miami Beach	Florida
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 Center	Missoula	Montana
United States	Monroe Cancer Center	Monroe	Michigan
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Intermountain Medical Center	Murray	Utah
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Licking Memorial Hospital	Newark	Ohio
United States	Newark Radiation Oncology	Newark	Ohio
United States	Chancellor Center for Oncology	Newburgh	Indiana
United States	USC Norris Oncology/Hematology-Newport Beach	Newport Beach	California
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	McKay-Dee Hospital Center	Ogden	Utah
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	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Menorah Medical Center	Overland Park	Kansas
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Parker Adventist Hospital	Parker	Colorado
United States	Keck Medical Center of USC Pasadena	Pasadena	California
United States	Singing River Hospital	Pascagoula	Mississippi
United States	Mercy Health Perrysburg Cancer Center	Perrysburg	Ohio
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
United States	Jefferson Healthcare	Port Townsend	Washington
United States	Southern Ohio Medical Center	Portsmouth	Ohio
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	Utah Valley Regional Medical Center	Provo	Utah
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Riverton Hospital	Riverton	Utah
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Saint George Regional Medical Center	Saint George	Utah
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	Saint Louis Cancer and Breast Institute-South City	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	Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Low Country Cancer Care	Savannah	Georgia
United States	Summit Cancer Care-Candler	Savannah	Georgia
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Henry Ford Macomb Health Center - Shelby Township	Shelby	Michigan
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Saint Michael Cancer Center	Silverdale	Washington
United States	South Jordan Health Center	South Jordan	Utah
United States	City of Hope South Pasadena	South Pasadena	California
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - North	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Valley	Spokane Valley	Washington
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Lakeview Hospital	Stillwater	Minnesota
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Moffitt Cancer Center - McKinley Campus	Tampa	Florida
United States	Moffitt Cancer Center-International Plaza	Tampa	Florida
United States	National Jewish Health-Northern Hematology Oncology	Thornton	Colorado
United States	Mercy Health - Saint Anne Hospital	Toledo	Ohio
United States	Mercy Health - Saint Vincent Hospital	Toledo	Ohio
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	City of Hope Upland	Upland	California
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Epic Care Cyberknife Center	Walnut Creek	California
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Mercy Hospital Washington	Washington	Missouri
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Saint Ann's Hospital	Westerville	Ohio
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	Rush-Copley Healthcare Center	Yorkville	Illinois
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

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	Baseline Mutational Load (Cohort A and B)	Will assess the association between per megabase mutation rate and pCR or CR status.	Up to 5 years
Other	Change in T-cell Infiltration (Cohort A and B)	Will compare change in CD8 expression following treatment between responders and non-responders.	Up to 5 years
Other	ctDNA Fraction	Will assess the association between response and ctDNA fraction.	Up to 5 years
Other	Clonality of Tumor Infiltrating T Cells (Cohort A and B)	Will compare change from baseline in TCR clonality metric between responders and non-responders.	Up to 5 years
Other	Adaptive Immune Resistant Mechanism (Cohort A and B)	Will compare change in PD-L1 expression between responders and non-responders.	Up to 5 years
Primary	Pathologic Complete Response (pCR) Rate (Cohort A)	Pathologic complete response is defined as no evidence of viable tumor cells on complete pathological evaluation of the surgical specimen per institutional standard of care.	Up to 5 years
Primary	Complete Response (CR) Rate (Cohort B)	Complete response (per RECIST 1.1) defined as: disappearance of all target and non-target lesions no new lesions, no disease related symptoms, and any lymph nodes must have reduction in short axis to < 1.0 cm.	Up to 5 years
Secondary	9 Week Response Rate (Cohort A)	Unconfirmed complete (CR) and partial responses (PR) at end of neoadjuvant treatment assessment among patients with measurable disease. CR and PR per response evaluation criteria in solid tumors (RECIST v1.1): CR is complete disappearance of all target and non-target lesions, no new lesions, no disease related symptoms, and lymph nodes must have reduction in short axis to <1.0cm. PR is greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions, no unequivocal progression of non-measurable disease, and no new lesions. Overall response = CR + PR.	Up to 3 months
Secondary	Overall Survival (Cohort A and B)	From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.	Up to 5 years
Secondary	Progression Free Survival (Cohort B)	From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last contact. Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm, unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided), appearance of any new lesion/site, or death due to disease without prior documentation of progression and without symptomatic deterioration	Up to 5 years
Secondary	Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs	Only adverse events that are possibly, probably or definitely related to study drug are reported. CTCAE Version 4.0 was used for all AE reporting.	Duration of treatment and follow-up until death or 5 years post registration.