Nivolumab With or Without Ipilimumab in Treating Patients With Persistent or Recurrent Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
Condition: Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma
MeSH terms: Carcinoma; Fallopian Tube Neoplasms; Recurrence
Intervention: Ipilimumab; Nivolumab
Intervention description: Given IV; Given IV
Intervention MeSH terms: Nivolumab; Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 100.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Phase II Randomized Trial of Nivolumab with or without Ipilimumab in Patients with Persistent or Recurrent Epithelial Ovarian; Primary Peritoneal or Fallopian; Tube Cancer

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.
    

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