A Study Evaluating Whether Pembrolizumab Alone or in Combination With CMP-001 Improves Efficacy in Patients With Operable Melanoma

Clinical Stage III Cutaneous Melanoma AJCC v8 Clinical Trial

Official title:

Phase II Randomized Study of Neoadjuvant Pembrolizumab Alone or in Combination With CMP-001 in Patients With Operable Melanoma: Efficacy and Biomarker Study

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04708418
• Other study ID #: NCI-2020-14174
• Secondary ID: NCI-2020-14174EA
• Status: Suspended
• Phase: Phase 2
• Start date: October 15, 2021
• Est. completion date: December 31, 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 the effect of pembrolizumab alone or in combination with CMP-001 in treating patients with melanoma that can be treated by surgery (operable). 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. Immunotherapy with CMP-001 may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. The addition of CMP-001 to pembrolizumab could improve the ability of the immune system to shrink tumors and to prevent them from returning.

Description:

PRIMARY OBJECTIVE: I. To evaluate the rate of pathologic complete response (pCR) rate in patients in each arm. SECONDARY OBJECTIVES: I. To evaluate the rate of pathologic near-complete/major response (pMR) of the neoadjuvant therapy in each arm. II. To evaluate the pathologic response rate of un-injected lesions on the combination arm (Arm B). III. To evaluate relapse-free survival (RFS) in each arm. IV. To evaluate overall survival (OS) in each arm. V. To evaluate the preoperative radiographic response rate in each arm. VI. To evaluate safety and toxicity of neoadjuvant therapy in each arm. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: NEOADJUVANT PHASE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo surgery 1-2 weeks after completion of neoadjuvant phase. ADJUVANT PHASE: After recovery from surgery, patients receive pembrolizumab IV over 30 minutes on day 1 of every other cycle. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or positron emission tomography (PET)/CT throughout the trial and may undergo optional biopsy at baseline and disease progression and optional collection of blood samples throughout the trial. ARM B: NEOADJUVANT PHASE: Patients receive VLP-encapsulated TLR9 agonist CMP-001 (CMP-001) subcutaneously (SC) on day 1 of cycle 1 and then intratumorally on days 8 and 15 of cycle 1, days 1, 8, and 15 of cycle 2, and day 1 of cycle 3. Patients also receive pembrolizumab IV over 30 minutes on day 8 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo surgery 1-2 weeks after completion of neoadjuvant phase. ADJUVANT PHASE: After recovery from surgery, patients receive pembrolizumab IV over 30 minutes on day 1 of every other cycle. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET/CT throughout the trial and may undergo optional biopsy at baseline and disease progression and optional collection of blood samples throughout the trial. After completion of study treatment, patients are followed up at 30 days and then every 3 months if < 2 years from study entry, every 6 months if 2-5 years from study entry, and every 12 months if > 5 years from study entry for up to 10 years (15 years total follow up).

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 60
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 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 of 0 or 1
• Patient must have a histologic diagnosis of melanoma belonging to the following

American Joint Committee on Cancer (AJCC) 8th edition TNM stages:

• T0, Tx or T1-4; and
• N1b, N2b, N2c, N3b or N3c
• Patients may have a presentation with primary melanoma with concurrent regional nodal and/or in-transit metastasis; or patients may have a history of primary melanoma or unknown primary melanoma presenting with clinically detected regional nodal and/or

in-transit recurrence; and may belong to any of the following groups:

• Primary cutaneous melanoma with clinically apparent regional lymph node metastases and/or in-transit metastases
• Clinically detected recurrent melanoma at the proximal regional lymph node(s) basin
• Primary cutaneous melanoma with concurrent nodal disease involving a single (or multiple) regional nodal group(s) if considered potentially surgically resectable at baseline
• Clinically detected nodal melanoma (if single site) arising from an unknown primary
• In-transit cutaneous metastases with or without regional lymph node involvement permitted if considered potentially surgically resectable at baseline
• NOTE: Patients with mucosal and/or uveal melanoma are not eligible for the study
• Patient must be a candidate for definitive surgery and have met with the treating surgical oncologist prior to randomization
• Patient must not have received any live vaccine within 30 days prior to randomization and while participating in the study. Live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine. Patients are permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and COVID-19 (Note: intranasal influenza vaccines, such as Flu-Mist [registered trademark] are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily, in order to minimize an overlap of adverse events)
• Patient must have the presence of injectable and measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, documented by scans obtained within 4 weeks prior to randomization
• NOTE: Injectable disease is defined as an accessible lesion in the skin, subcutaneous tissue or lymph nodes (LN) close to the skin and palpable by physical examination or approachable with ultrasound guidance
• Absolute neutrophil count (ANC) >= 1,500 /mcL (obtained within 4 weeks prior to randomization)
• Hemoglobin (Hgb) >= 9 g/dL or >= 5.6 mmol/L (obtained within 4 weeks prior to randomization)
• Platelets >= 100,000 / mcL (obtained within 4 weeks prior to randomization)
• Serum creatinine =< 1.5 x institutional upper limit of normal (ULN) or measured or calculated creatinine clearance > 60 mL/min (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl] for patients with creatinine levels > 1.5 x institutional ULN) (obtained within 4 weeks prior to randomization)
• Serum total bilirubin =< 1.5 x institutional ULN; for total bilirubin level > 1.5 x ULN but =< 3 x ULN, the direct bilirubin must be =< the institutional ULN (obtained within 4 weeks prior to randomization)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 4 weeks prior to randomization)
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x institutional ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (obtained within 4 weeks prior to randomization)
• Activated partial thromboplastin time (aPTT) =< 1.5 x institutional ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (obtained within 4 weeks prior to randomization)
• Patients 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. All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A urine or serum pregnancy test must be repeated within 72 hours prior to receiving the first dose of pembrolizumab if the test done for eligibility/randomization is done outside of this 72 hour window. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. A patient of childbearing potential is defined as anyone, 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)
• Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or abstaining from sexual intercourse from time of randomization, while on study treatment, and continue for 26 weeks after the last dose of protocol treatment
• Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients 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
• Patient must not have received prior systemic therapy for melanoma including systemic therapy with an anti-PD-1, anti-PD-L1, anti-CTLA-4, BRAF/MEK inhibitor combination and/or TLR-9 agonist
• Patient must not have a diagnosis of immunodeficiency or be receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization, except as noted here
• Patients who are currently receiving steroids at a dose of prednisone =< 5 mg daily (or equivalent) are permitted to enroll
• Patients who require topical, ophthalmologic and inhalational steroids are permitted to enroll
• Patients with hypothyroidism who are stable on hormone replacement are permitted to enroll
• Patients who require active immunosuppression with corticosteroids at a dose of prednisone > 5 mg daily (or equivalent) for any reason are ineligible
• Patients with adrenal insufficiency are ineligible
• Patients who have developed autoimmune disorders of grade 4 while on prior immunotherapy are not permitted to enroll on this study. Patients who developed autoimmune disorders of grade =< 3 may enroll if the disorder has resolved to grade =< 1 and the patient has been off systemic corticosteroids at doses > 5 mg for at least 2 weeks prior to randomization
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to randomization are eligible for this trial
• 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 with a history of brain metastases are not eligible for this study as they do not meet the eligibility staging criteria
• 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
• Patient must not have had an allogeneic tissue/solid organ transplant
• Patient must not have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Patient must not have severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
• Patient must not have an active infection requiring systemic therapy
• Patient must not have a known psychiatric or substance abuse disorder that would interfere with the patient's ability to cooperate with the requirements of the study

Related Conditions & MeSH terms

• Clinical Stage III Cutaneous Melanoma AJCC v8
• Melanoma
• Melanoma of Unknown Primary
• Pathologic Stage IIIB Cutaneous Melanoma AJCC v8
• Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
• Pathologic Stage IIID Cutaneous Melanoma AJCC v8
• Recurrent Cutaneous Melanoma
• Skin Neoplasms

Intervention

Procedure:
• Biopsy
Undergo biopsy
• Biospecimen Collection
Undergo collection of blood samples
• Computed Tomography
Undergo CT or PET/CT

Biological:
• Pembrolizumab
Given IV

Procedure:
• Positron Emission Tomography
Undergo PET/CT
• Surgical Procedure
Undergo surgery

Drug:
• VLP-encapsulated TLR9 Agonist CMP-001
Given SC or intratumorally

Locations

Country	Name	City	State
United States	Avera Cancer Institute-Aberdeen	Aberdeen	South Dakota
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Saint Luke's Cancer Center - Allentown	Allentown	Pennsylvania
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
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	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	The Medical Center of Aurora	Aurora	Colorado
United States	UM Sylvester Comprehensive Cancer Center at Aventura	Aventura	Florida
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Louisiana Hematology Oncology Associates LLC	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Saint Charles Health System	Bend	Oregon
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
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	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Illinois CancerCare-Canton	Canton	Illinois
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	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Rocky Mountain Cancer Centers - Centennial	Centennial	Colorado
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	University of Virginia Cancer Center	Charlottesville	Virginia
United States	University of Illinois	Chicago	Illinois
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Bay Area Hospital	Coos Bay	Oregon
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
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	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	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	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Epic Care-Dublin	Dublin	California
United States	Saint Luke's Hospital-Anderson Campus	Easton	Pennsylvania
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Bay Area Breast Surgeons Inc	Emeryville	California
United States	Epic Care Partners in Cancer Care	Emeryville	California
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Rocky Mountain Cancer Centers - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	The Melanoma and Skin Cancer Institute	Englewood	Colorado
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
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	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	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	North Colorado Medical Center	Greeley	Colorado
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Wayne Hospital	Greenville	Ohio
United States	Terrebonne General Medical Center	Houma	Louisiana
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
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	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
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	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	McKee Medical Center	Loveland	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
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	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Corewell Health Lakeland Hospitals - Niles Hospital	Niles	Michigan
United States	Cancer and Hematology Centers of Western Michigan - Norton Shores	Norton Shores	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Tumor Institute	Oakland	California
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	Saint Joseph Hospital - Orange	Orange	California
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
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	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida
United States	Jefferson Healthcare	Port Townsend	Washington
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Saint Luke's Hospital-Quakertown Campus	Quakertown	Pennsylvania
United States	Corewell Health Reed City Hospital	Reed City	Michigan
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Reid Health	Richmond	Indiana
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
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	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
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	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
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	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Epic Care Cyberknife Center	Walnut Creek	California
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Michigan Health - West	Wyoming	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
Primary	Pathologic complete response rate	Will be estimated by the percentage of patients who achieve complete response, partial response or stable disease by Response Evaluation Criteria in Solid Tumors (RECIST) and Immune-Modified (i)RECIST criteria, with exact 90% confidence intervals.	Up to 15 years
Secondary	Radiographic response rate	Will be assessed using RECIST.	Up to 15 years
Secondary	Relapse-free survival		From randomization to relapse or death (whichever occurs first), assessed up to 15 years
Secondary	Overall survival		From randomization to death from any cause, assessed up to 15 years
Secondary	Incidence of adverse events	Patients will be monitored for adverse events using the National Cancer Institute's Common Terminology Criteria for Adverse Events.	Up to 30 days after the last study drug administration