Pembrolizumab, Cisplatin, and Rintatolimod in Treating Patients with Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Inclusion Criteria

• Patients with recurrent platinum sensitive ovarian cancer (OC).
• Patients must have first or second peritoneal recurrence of epithelial adenocarcinoma or carcinosarcoma of ovarian, tubal or peritoneal origin: * Histologic documentation of the original primary tumor is required via the pathology report. * Original tumor blocks from the primary diagnosis will be requested by our study pathologist at Magee-Women’s Hospital of University of Pittsburgh Medical Center (UPMC) Cancer Centers. Original tumor blocks may be reviewed after registration (informed consent and enrollment).
• Patients must have completed prior platinum-based therapy. Response can be complete or partial if it otherwise meets platinum sensitive criteria.
• Patients must be platinum-sensitive, defined as having a progression free interval (PFI) of more than 6 months (180 days) from any platinum therapy. Patients are allowed to have had other lines of therapy since last platinum if PFI after platinum therapy meets platinum sensitive criteria.
• Patients must have measurable disease in the peritoneal cavity, measurable per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria: * A mass with a length of 1.0 cm or greater and/or * A lymph node with a length of 1.5 cm or greater in the shortest axis.
• Patients must be a reasonable candidate for laparoscopy and IP platinum regimen with no prior evidence of clinically significant intra-abdominal adhesions, persistent abdominal wall infections, renal toxicity or bowel obstruction.
• Patients of childbearing potential must: * Have a negative pregnancy test prior to the study entry. * Must discontinue breastfeeding prior to the first date of treatment on this study if applicable. * Agree to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
• Patients must agree to the protocol designated clinical monitoring to receive the study regimens.
• The participant provides written informed consent for the trial.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation/randomization.
• Absolute neutrophil count (ANC) >= 1500/uL (collected within 14 days prior to the start of study treatment).
• Platelets >= 100,000/uL (collected within 14 days prior to the start of study treatment).
• Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (collected within 14 days prior to the start of study treatment).
• Creatinine =< 1.5 upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30 mL/min with creatinine levels > 1.5 institutional ULN (collected within 14 days prior to the start of study treatment).
• Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN (collected within 14 days prior to the start of study treatment).
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (=< 5 x ULN for participants with liver metastases) (collected within 14 days prior to the start of study treatment).
• International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants (collected within 14 days prior to the start of study treatment).
• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants (collected within 14 days prior to the start of study treatment).

Exclusion Criteria

• A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to infusion of treatment regimen. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation. * Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to =< grade 1 or baseline. Participants with =< grade 2 neuropathy may be eligible. * Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=< 2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Patients who received maintenance therapy after the prior platinum therapy. An exception to this exclusion would be if the PFI is greater than 6 months (180 days) off of the maintenance agent or a PFI greater than a 1 year (365 days) regardless of the duration of maintenance therapy.
• Patients with previous pelvic radiation therapy.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. * Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Patients with tumors of low malignant potential, except ovarian pseudomyxomas, or with no peritoneal disease.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. * Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients.
• Has a known allergy to cisplatin chemotherapy. Patients with carboplatin allergy may be included if they tolerate a test dose of IV cisplatin given in monitored floor conditions.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a known history of human immunodeficiency virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA] qualitative is detected) infection. Note: no testing for hepatitis B and hepatitis C is required unless mandated by local health authority.
• Has a known history of active TB (Bacillus tuberculosis).
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.