Systemic Immune Checkpoint Blockade and Intraperitoneal Chemo-Immunotherapy in Recurrent Ovarian Cancer
- Conditions
- Ovarian Cancer Recurrent
- Interventions
- Registration Number
- NCT03734692
- Lead Sponsor
- Robert Edwards
- Brief Summary
This is a phase II single arm efficacy/safety trial that will evaluate the effectiveness of combining intensive locoregional intraperitoneal (IP) chemoimmunotherapy of cisplatin with IP rintatolimod (TLR-3 agonist) and IV infusion of the checkpoint inhibitor pembrolizumab (IVP) for patients with recurrent platinum-sensitive ovarian cancer (OC).
- Detailed Description
Patients will receive a total of six treatment cycles, at 3-week intervals. The study will use an IP neoadjuvant approach (IP chemoimmunotherapy of cisplatin with IP rintatolimod and IV infusion of pembrolizumab), followed by interval cytoreduction (usually laparoscopically) of residual tumor. Cytoreduction will occur approximately 4 weeks after the fourth treatment cycle. Post-surgery the investigators will consolidate with 2 additional courses of same chemo-immunotherapy regimen. Catheter will be removed 12 weeks after the last treatment. All surgical procedures, if done laparoscopically, are outpatient and will yield up to three serial biopsies of the tumor sites: 1) at catheter placement; 2) at interval cytoreduction which consists of removal of any visible tumor sites and the site biopsied initially whether tumor is present or not; 3) at catheter removal, when site of first tumor biopsy will be re-biopsied for pathologic response.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description cisplatin + rintatolimod + pembrolizumab Rintatolimod Intraperitoneal (IP) cisplatin 50mg/m\^2 solution with IP rintatolimod 200 mg solution and IV pembrolizumab 200 mg solution. cisplatin + rintatolimod + pembrolizumab Pembrolizumab Intraperitoneal (IP) cisplatin 50mg/m\^2 solution with IP rintatolimod 200 mg solution and IV pembrolizumab 200 mg solution. cisplatin + rintatolimod + pembrolizumab Cisplatin Intraperitoneal (IP) cisplatin 50mg/m\^2 solution with IP rintatolimod 200 mg solution and IV pembrolizumab 200 mg solution.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) At 13 weeks The proportion of subjects with the best response of complete response (CR), or partial response (PR) per Response Evaluation Criteria for Solid Tumors (RECIST 1.1). Per RECIST 1.1 , CR is defined as all target lesions gone; PR is defined as a \> 30% decrease in size of lesion from baseline.
- Secondary Outcome Measures
Name Time Method DLTs Related to Treatment At baseline (pre-treatment) and at 12 weeks (after the start of treatment) Number of patients who experience Adverse Events per CTCAE v5.0 related to study treatment, including any death not clearly due to disease or extraneous causes, AE leading to a dose delay of greater than 14 days in initiation of cycle 2, a DLT occurring during Cycle 1 of treatment: Grade ≥ 3 renal toxicity, diarrhea, skin toxicity, injection site reactions, anaphylaxis, hematologic toxicities lasting more than 48 hours (including neutropenia), non-hematologic toxicities, neurological symptoms, thrombocytopenia and hemorrhage, liver function test increase; Grade ≥ 2 or greater bronchospasm, allergic reaction or generalized urticaria, autoimmune reaction, pneumonitis; Fever \> 41°C, uncontrolled for over 4 hours in the absence of a medical cause Evaluation of liver toxicity per Hy's Law: Drug causes hepatocellular injury (higher incidence of 3-fold or greater elevations above the ULN of ALT or AST); Total Bilirubin\>2xULN (without initial cholestasis (elevated serum alkaline phosphatase)
Progression-Free Survival (PFS) up to 4 years The length of time during and after study treatment that a patient does not experience worsening disease. Per RECIST 1.1 or dies from any cause. Progression is defined as a \> 20% increase from smallest sum of longest (lesion) diameter recorded since treatment started (best response - target lesions) and/or, enlargement of non-target lesions.
Time To Disease Progression up to 4 years The length of time during and after study treatment that a patient remains alive without worsening disease. Per RECIST 1.1, progression is defined as a \> 20% increase from smallest sum of longest (lesion) diameter recorded since treatment started (best response - target lesions) and/or, enlargement of non-target lesions.
Change in Number of CD8+ Cells At baseline (pre-treatment) and at 8 weeks (after the start of treatment) Within-patient changes in number of CD8+ cells present in tumor tissue and peritoneal fluid.
Change in Number of CD3+ Cells at baseline (pre-treatment) and at 12 weeks (after the start of treatment) Within-patient changes in number of CD3+ cells present in tumor tissue and peritoneal fluid.
Trial Locations
- Locations (1)
Magee-Womens Hospital of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Magee-Womens Hospital of UPMC🇺🇸Pittsburgh, Pennsylvania, United States