Nivolumab With or Without Ipilimumab in Treating Patients With Persistent or Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma
About this trial
This is an interventional treatment trial for Recurrent Fallopian Tube Carcinoma focused on measuring Phase II Randomized Trial of Nivolumab with or without Ipilimumab in Patients with Persistent or Recurrent Epithelial Ovarian, Primary Peritoneal or Fallopian, Tube Cancer
Eligibility Criteria
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
Sites / Locations
- Sutter Auburn Faith Hospital
- Sutter Cancer Centers Radiation Oncology Services-Auburn
- Alta Bates Summit Medical Center-Herrick Campus
- Sutter Cancer Centers Radiation Oncology Services-Cameron Park
- Sutter Davis Hospital
- Palo Alto Medical Foundation-Gynecologic Oncology
- Palo Alto Medical Foundation Health Care
- Sutter Cancer Centers Radiation Oncology Services-Roseville
- Sutter Roseville Medical Center
- Sutter Medical Center Sacramento
- California Pacific Medical Center-Pacific Campus
- UCSF Medical Center-Mission Bay
- Palo Alto Medical Foundation-Santa Cruz
- Sutter Cancer Centers Radiation Oncology Services-Vacaville
- Rocky Mountain Cancer Centers-Aurora
- Boulder Community Hospital
- Rocky Mountain Cancer Centers-Boulder
- Penrose-Saint Francis Healthcare
- Rocky Mountain Cancer Centers-Penrose
- UCHealth Memorial Hospital Central
- Denver Health Medical Center
- Porter Adventist Hospital
- Colorado Blood Cancer Institute
- Presbyterian - Saint Lukes Medical Center - Health One
- Rocky Mountain Cancer Centers-Midtown
- SCL Health Saint Joseph Hospital
- Rocky Mountain Cancer Centers-Rose
- Rose Medical Center
- Mercy Medical Center
- Southwest Oncology PC
- Mountain Blue Cancer Care Center - Swedish
- Swedish Medical Center
- Poudre Valley Hospital
- Mountain Blue Cancer Care Center
- National Jewish Health-Western Hematology Oncology
- North Colorado Medical Center
- Rocky Mountain Cancer Centers-Greenwood Village
- Rocky Mountain Cancer Centers-Lakewood
- Saint Anthony Hospital
- Rocky Mountain Cancer Centers-Littleton
- Littleton Adventist Hospital
- Rocky Mountain Cancer Centers-Sky Ridge
- Longmont United Hospital
- Rocky Mountain Cancer Centers-Longmont
- McKee Medical Center
- Parker Adventist Hospital
- Rocky Mountain Cancer Centers-Parker
- Saint Mary Corwin Medical Center
- Rocky Mountain Cancer Centers - Pueblo
- Rocky Mountain Cancer Centers-Thornton
- SCL Health Lutheran Medical Center
- Yale University
- Christiana Gynecologic Oncology LLC
- Helen F Graham Cancer Center
- Christiana Care Health System-Christiana Hospital
- Sibley Memorial Hospital
- Dekalb Medical Center
- Memorial Health University Medical Center
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Rush - Copley Medical Center
- University of Chicago Comprehensive Cancer Center
- Carle at The Riverfront
- Carle Physician Group-Effingham
- Northwestern Medicine Cancer Center Delnor
- Sudarshan K Sharma MD Limited-Gynecologic Oncology
- Carle Physician Group-Mattoon/Charleston
- Good Samaritan Regional Health Center
- Carle Cancer Center
- The Carle Foundation Hospital
- Northwestern Medicine Cancer Center Warrenville
- Rush-Copley Healthcare Center
- Ascension Saint Vincent Indianapolis Hospital
- Franciscan Saint Anthony Health-Michigan City
- Woodland Cancer Care Center
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Cancer Center-West Lakes
- Alegent Health Mercy Hospital
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- University of Iowa/Holden Comprehensive Cancer Center
- Mercy Medical Center-West Lakes
- Flaget Memorial Hospital
- Commonwealth Cancer Center-Corbin
- Saint Joseph Radiation Oncology Resource Center
- Saint Joseph Hospital East
- Jewish Hospital
- Saints Mary and Elizabeth Hospital
- UofL Health Medical Center Northeast
- Jewish Hospital Medical Center South
- Maine Medical Center- Scarborough Campus
- Greater Baltimore Medical Center
- Sinai Hospital of Baltimore
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Northwest Hospital Center
- Tufts Medical Center
- Henry Ford Cancer Institute-Downriver
- Henry Ford Macomb Hospital-Clinton Township
- Henry Ford Medical Center-Fairlane
- Wayne State University/Karmanos Cancer Institute
- Henry Ford Hospital
- Spectrum Health at Butterworth Campus
- West Michigan Cancer Center
- Henry Ford Medical Center-Columbus
- Spectrum Health Reed City Hospital
- Munson Medical Center
- Henry Ford West Bloomfield Hospital
- Sanford Joe Lueken Cancer Center
- Central Care Cancer Center - Bolivar
- Cox Cancer Center Branson
- Mercy Hospital Joplin
- Mercy Clinic-Rolla-Cancer and Hematology
- Saint Louis Cancer and Breast Institute-South City
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- Mercy Hospital Springfield
- CoxHealth South Hospital
- CHI Health Saint Francis
- Heartland Hematology and Oncology
- CHI Health Good Samaritan
- Saint Elizabeth Regional Medical Center
- Nebraska Methodist Hospital
- Alegent Health Immanuel Medical Center
- Hematology and Oncology Consultants PC
- Alegent Health Bergan Mercy Medical Center
- Alegent Health Lakeside Hospital
- Creighton University Medical Center
- Midlands Community Hospital
- Women's Cancer Center of Nevada
- Wentworth-Douglass Hospital
- Memorial Sloan Kettering Basking Ridge
- Memorial Sloan Kettering Monmouth
- Inspira Medical Center Vineland
- Memorial Sloan Kettering Commack
- Memorial Sloan Kettering Westchester
- Memorial Sloan Kettering Cancer Center
- Memorial Sloan Kettering Sleepy Hollow
- Memorial Sloan Kettering Nassau
- Randolph Hospital
- Cone Health Cancer Center at Alamance Regional
- Cone Health Cancer Center
- Hendersonville Hematology and Oncology at Pardee
- Margaret R Pardee Memorial Hospital
- Cone Heath Cancer Center at Mebane
- Annie Penn Memorial Hospital
- Sanford Bismarck Medical Center
- Sanford Broadway Medical Center
- Sanford Clinic North-Fargo
- Sanford Roger Maris Cancer Center
- Trinity Cancer Care Center
- Cleveland Clinic Akron General
- UHHS-Chagrin Highlands Medical Center
- Good Samaritan Hospital - Cincinnati
- Bethesda North Hospital
- TriHealth Cancer Institute-Westside
- TriHealth Cancer Institute-Anderson
- Case Western Reserve University
- Cleveland Clinic Cancer Center/Fairview Hospital
- Cleveland Clinic Foundation
- Hillcrest Hospital Cancer Center
- UH Seidman Cancer Center at Landerbrook Health Center
- University Hospitals Sharon Health Center
- UHHS-Westlake Medical Center
- University of Oklahoma Health Sciences Center
- Oklahoma Cancer Specialists and Research Institute-Tulsa
- Jefferson Abington Hospital
- Lehigh Valley Hospital-Cedar Crest
- Saint Luke's University Hospital-Bethlehem Campus
- University of Pennsylvania/Abramson Cancer Center
- Chester County Hospital
- Women and Infants Hospital
- Prisma Health Cancer Institute - Spartanburg
- Prisma Health Cancer Institute - Easley
- Gibbs Cancer Center-Gaffney
- Greenville Health System Cancer Institute-Andrews
- Prisma Health Cancer Institute - Butternut
- Prisma Health Cancer Institute - Faris
- Prisma Health Greenville Memorial Hospital
- Saint Francis Cancer Center
- Prisma Health Cancer Institute - Eastside
- Prisma Health Cancer Institute - Greer
- Gibbs Cancer Center-Pelham
- Prisma Health Cancer Institute - Seneca
- Spartanburg Medical Center
- MGC Hematology Oncology-Union
- Sanford Cancer Center Oncology Clinic
- Sanford USD Medical Center - Sioux Falls
- Memorial Hospital
- Pulmonary Medicine Center of Chattanooga-Hixson
- Memorial GYN Plus
- Parkland Memorial Hospital
- UT Southwestern/Simmons Cancer Center-Dallas
- Inova Fairfax Hospital
- Carilion Clinic Gynecological Oncology
- Harrison HealthPartners Hematology and Oncology-Bremerton
- Harrison Medical Center
- Highline Medical Center-Main Campus
- Saint Elizabeth Hospital
- Saint Francis Hospital
- Kadlec Clinic Hematology and Oncology
- Saint Clare Hospital
- Harrison HealthPartners Hematology and Oncology-Poulsbo
- FHCC South Lake Union
- Franciscan Research Center-Northwest Medical Plaza
- Northwest Medical Specialties PLLC
- Monongalia Hospital
- Medical College of Wisconsin
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Group I (nivolumab)
Group II (nivolumab, ipilimumab)
INDUCTION: Patients receive nivolumab 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.
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.