Nivolumab With or Without Ipilimumab in Treating Patients With Persistent or Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Recurrent Ovarian Carcinoma Clinical Trial

Official title:

Phase II Randomized Trial of Nivolumab With or Without Ipilimumab in Patients With Persistent or Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02498600
• Other study ID #: NCI-2014-02424
• Secondary ID: NCI-2014-02424NR
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 29, 2015
• 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 randomized phase II trial studies how well nivolumab works with or without ipilimumab in treating patients with epithelial ovarian, primary peritoneal, or fallopian tube cancer that has not responded after prior treatment (persistent) or has come back (recurrent). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, 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 OBJECTIVE:

I. To estimate the proportion of patients who have objective tumor response (complete or partial) by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in patients with persistent or recurrent epithelial ovarian, fallopian tube, primary peritoneal cancers, treated with nivolumab or the combination of nivolumab and ipilimumab and to assess the difference in objective response rate (ORR) between patients treated with nivolumab versus those treated with the combination of nivolumab and ipilimumab.

SECONDARY OBJECTIVES:

I. To estimate the progression-free survival (PFS) hazard ratio for patients treated with nivolumab versus those treated with the combination of nivolumab and ipilimumab.

II. To estimate and compare the duration of overall survival (OS) for patients treated with nivolumab or the combination of nivolumab and ipilimumab.

III. To determine the frequency and severity of adverse events associated with treatment with nivolumab or the combination of nivolumab and ipilimumab as assessed by Common Terminology Criteria for Adverse Events (CTCAE).

IV. To determine whether cellular and molecular laboratory parameters in pre-treatment tissue and peripheral blood specimens predict overall survival (OS), tumor response by modified RECIST 1.1, and progression-free survival (PFS):

IVa. PD-L1 expression in tumor cells and tumor-infiltrating lymphocytes (TILs) measured by quantitative immunohistochemistry (IHC).

IVb. Natural anti-tumor immunity in tumor cells and TILs measured using IHC and T cell repertoire analyses.

IVc. Tumor "immunogenicity" as determined by the neo-epitope landscape using next-generation whole exome sequencing (NGS).

IVd. Anti-tumor immune response in peripheral blood, including serologic responses and analysis of T cell receptor (TCR) repertoires by deep sequencing.

IVe. Shift in quantitative laboratory peripheral blood parameters after the first 6 and 12 weeks of therapy.

OUTLINE: Patients are randomized to 1 of 2 treatment groups.

GROUP I:

INDUCTION: Patients receive nivolumab intravenously (IV) over 30 minutes every 2 weeks. Treatment repeats every 4 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive nivolumab IV over 30 minutes every 2 weeks. Treatment repeats every 4 weeks for up to 21 cycles in the absence of disease progression or unacceptable toxicity.

GROUP II:

INDUCTION: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive nivolumab IV over 30 minutes every 2 weeks. Treatment repeats every 4 weeks for up to 21 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 100 days, every 3 months for 2 years, and then every 6 months for 3 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 31, 2024
• Est. primary completion date: September 5, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer with documented disease progression (disease not amendable to curative therapy); histologic confirmation of the original primary tumor is required via the pathology report; NOTE: patients with mucinous histology are NOT eligible; patients with carcinosarcoma histology are NOT eligible

• All patients must have measurable disease as defined by RECIST 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

• Patients must have at least one "target" lesion to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

• Appropriate for study entry based on the following diagnostic workup:

• History/physical examination within 28 days prior to registration

• Imaging of target lesion(s) within 28 days prior to registration

• Further protocol-specific assessments:

• Recovery from effects of recent surgery, radiotherapy or chemotherapy

• Free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])

• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration

• Any other prior therapy directed at the malignant tumor including chemotherapy, targeted agents, immunologic agents, and any investigational agents, must be discontinued at least 4 weeks prior to registration (6 weeks for nitrosoureas or mitomycin C)

• Any prior radiation therapy must be completed at least 4 weeks prior to registration

• At least 4 weeks must have elapsed since major surgery

• Patients are allowed to have received up to three prior cytotoxic regimens for treatment of their epithelial ovarian, fallopian tube, or primary peritoneal cancer; they must have had one prior platinum-based chemotherapeutic regimen for management of primary disease, possibly including intra-peritoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents or extended therapy (maintenance/consolidation) administered after surgical or non-surgical assessment; patients are allowed to have received, but are not required to have received, one to two cytotoxic regimens for management of recurrent or persistent disease; (for the purposes of this study poly adenosine diphosphate [ADP] ribose polymerase [PARP] inhibitors given for recurrent or progressive disease will be considered cytotoxic; PARP inhibitors given as maintenance therapy in continuation with management of primary disease will not be considered as a separate cytotoxic regimen); if two cytotoxic regimens had been received for management of recurrent or persistent disease, one of these regimens would have had to contain either a platinum or a taxane agent

• Performance status of 0, 1 or 2 within 28 days prior to registration

• Absolute neutrophil count (ANC) >= 1,500/ul (within 14 days prior to registration)

• Platelets >= 100,000/ul (within 14 days prior to registration)

• Creatinine =< 1.5 x institutional/laboratory upper limit of normal (ULN) (within 14 days prior to registration)

• Bilirubin =< 1.5 x ULN; for patients with Gilbert's syndrome, bilirubin =< 3.0 mg/dL is acceptable (within 14 days prior to registration)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (within 14 days prior to registration)

• Albumin >= 2.8 g/dL (within 14 days prior to registration)

• Adequate thyroid function within 28 days prior to registration defined as serum thyroid-stimulating hormone (TSH) in normal range

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

• Platinum-free interval (PFI) - patients must have progressed < 12 months after completion of their last platinum-based chemotherapy; the date (platinum free interval) should be calculated from the last administered dose of platinum therapy to documentation of progression

• Adequate oxygen saturation via pulse oximeter within 28 days prior to registration (i.e., patient can NOT have CTCAE hypoxia grade 2 or greater)

• Left ventricular ejection fraction (LVEF) >= 50% (measured within 28 days of study entry)

Exclusion Criteria:

• Patients who have had prior therapy with nivolumab or with an anti-programmed cell death (PD)-1, anti-PD-ligand (L)1, anti-PD-L2, anti-cytotoxic T-lymphocyte-antigen (CTLA)-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways

• History of severe hypersensitivity reaction to any monoclonal antibody

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies are excluded if there is any evidence of other malignancy being present within the last three years (2 years for breast cancer); patients are also excluded if their previous cancer treatment contraindicates this protocol therapy

• Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy and radiotherapy for localized breast cancer, provided that it was completed more than 2 years prior to registration, and the patient remains free of recurrent or metastatic disease and hormonal therapy has been discontinued; patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis or thoracic cavity within the last three years are excluded; prior radiation for localized cancer of the head and neck or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease

• Patients with uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure and unstable angina pectoris

• Patients with history of organ transplant

• Patients who are pregnant or nursing; women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; WOCBP should use an adequate method to avoid pregnancy for 23 weeks after the last dose of investigational drug; WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IV/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab or nivolumab + ipilimumab; women must not be breastfeeding; women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) do not require contraception; women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy and/or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 month amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level greater than 40 mIU/mL; if, following initiation of the investigational product(s), it is subsequently discovered that a study subject is pregnant or may have been pregnant at the time of investigational product exposure, including during at least 6 half-lives after product administration, the investigational product will be permanently discontinued in an appropriate manner (e.g., dose tapering if necessary for subject safety); the investigator must report this event and any outcomes by amendment through Cancer Therapy Evaluation Program (CTEP)-Adverse Event Reporting System (AERS); protocol-required procedures for study discontinuation and follow-up must be performed on the subject unless contraindicated by pregnancy (e.g., X-ray studies); other appropriate pregnancy follow-up procedures should be considered if indicated; in addition, the investigator must report and follow-up on information regarding the course of the pregnancy, including perinatal and neonatal outcome; infants should be followed for a minimum of 8 weeks

• History or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures which are not controlled with non-enzyme inducing anticonvulsants, any brain metastases and/or epidural disease, or history of cerebrovascular accident (cerebrovascular accident [CVA], stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months prior to the first date of study treatment

• In order for patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) to be eligible, they must be on a stable highly active antiretroviral therapy (HAART) regimen, have cluster of differentiation (CD)4 counts > 350, with no detectable viral load on quantitative polymerase chain reaction (PCR)

• Patients with treated hepatitis virus infections (hepatitis B or hepatitis C) are eligible if they have been definitively treated for 6 months, have no detectable viral load on quantitative PCR, and liver function tests (LFTs) meet eligibility requirements

• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease, Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded; patient with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible; patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible

• Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement (such as Hashimoto's thyroiditis), psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)

• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses =< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted

• Any of the following within 2 months of registration: active peptic ulcer disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, malabsorption syndrome; any of the following within 6 months of registration: intra-abdominal abscess, gastrointestinal obstruction requiring parenteral hydration and/or nutrition, gastrointestinal perforation; Note: complete resolution of an intra-abdominal abscess must be confirmed prior to registration even if the abscess occurred more than 6 months prior to registration

• No planned concomitant, non-protocol directed anti-cancer therapy

• Grade >= 2 peripheral neuropathy

Related Conditions & MeSH terms

• Carcinoma
• Fallopian Tube Neoplasms
• Recurrence
• Recurrent Fallopian Tube Carcinoma
• Recurrent Ovarian Carcinoma
• Recurrent Primary Peritoneal Carcinoma

Intervention

Biological:
• Ipilimumab
Given IV
• Nivolumab
Given IV

Locations

Country	Name	City	State
United States	Jefferson Abington Hospital	Abington	Pennsylvania
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Randolph Hospital	Asheboro	North Carolina
United States	Sutter Auburn Faith Hospital	Auburn	California
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Tufts Medical Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
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	Highline Medical Center-Main Campus	Burien	Washington
United States	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Memorial Hospital	Chattanooga	Tennessee
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
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	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
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	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	Memorial Sloan Kettering Commack	Commack	New York
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Carle at The Riverfront	Danville	Illinois
United States	Sutter Davis Hospital	Davis	California
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Dekalb Medical Center	Decatur	Georgia
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Denver Health Medical Center	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	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	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Wentworth-Douglass Hospital	Dover	New Hampshire
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	Carle Physician Group-Effingham	Effingham	Illinois
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	Inova Fairfax Hospital	Falls Church	Virginia
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Saint Francis Hospital	Federal Way	Washington
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	National Jewish Health-Western Hematology Oncology	Golden	Colorado
United States	Nebraska Cancer Specialists/Oncology Hematology West PC	Grand Island	Nebraska
United States	Corewell Health Grand Rapids Hospitals - Butterworth Hospital	Grand Rapids	Michigan
United States	Banner North Colorado Medical Center	Greeley	Colorado
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Greenville Health System Cancer Institute-Andrews	Greenville	South 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	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Hendersonville Hematology and Oncology at Pardee	Hendersonville	North Carolina
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Sudarshan K Sharma MD Limited-Gynecologic Oncology	Hinsdale	Illinois
United States	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee
United States	Ascension Saint Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Heartland Hematology and Oncology	Kearney	Nebraska
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
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	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
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	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	UH Seidman Cancer Center at Landerbrook Health Center	Mayfield Heights	Ohio
United States	Cone Heath Cancer Center at Mebane	Mebane	North Carolina
United States	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana
United States	Woodland Cancer Care Center	Michigan City	Indiana
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Trinity Cancer Care Center	Minot	North Dakota
United States	Monongalia Hospital	Morgantown	West Virginia
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Christiana Gynecologic Oncology LLC	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
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	Hematology and Oncology Consultants PC	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Memorial GYN Plus	Ooltewah	Tennessee
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	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Northwest Hospital Center	Randallstown	Maryland
United States	Corewell Health Reed City Hospital	Reed City	Michigan
United States	Annie Penn Memorial Hospital	Reidsville	North Carolina
United States	Carilion Clinic Gynecological Oncology	Roanoke	Virginia
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
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	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	FHCC South Lake Union	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Saint Michael Cancer Center	Silverdale	Washington
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Sloan Kettering Sleepy Hollow	Sleepy Hollow	New York
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	Munson Medical Center	Traverse City	Michigan
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	MGC Hematology Oncology-Union	Union	South Carolina
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Inspira Medical Center Vineland	Vineland	New Jersey
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Chester County Hospital	West Chester	Pennsylvania
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Rush-Copley Healthcare Center	Yorkville	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Natural Anti-tumor Immunity in Tumor Infiltrating Lymphocytes and Tumor Cells	Assessed with immunohistochemistry.	Baseline
Other	Markers of "Immunogenicity"	Determined by the neo-epitope landscape using next-generation whole exome sequencing.	Baseline
Other	Changes in Biomarkers	Will assess the impact of biomarkers on tumor response, PFS, and OS.	Baseline to after the first 8 weeks of therapy
Primary	Objective Tumor Response	Complete and Partial Tumor Response by modified irRECIST. Per Response Evaluation Criteria In Solid Tumors Criteria (irRECIST) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Within 6 months of study entry
Secondary	Progression-free Survival (PFS)	Time until disease progression, death, or date of last contact. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (irRECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	The duration of time from study entry to time of progression or death, whichever occurs first, an average of 3.9 months.
Secondary	Duration of Overall Survival (OS)	The observed length of life from randomization into the study to death or the date of last contact.	The duration of time from study entry to time of death or the date of last contact, assessed up to 5 years
Secondary	Incidence of Adverse Events Grade 3 and Above	Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	Up to 30 days after treatment ends