Systemic Immune Checkpoint Blockade and Intraperitoneal Chemo-Immunotherapy in Recurrent Ovarian Cancer

Phase 1

Recruiting

• Conditions: Ovarian Cancer Recurrent
• Interventions: Drug: Rintatolimod; Drug: Pembrolizumab; Drug: Cisplatin

• 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.

Study Timeline

• Study First Submitted: 2018-11-06
• Study First Submitted QC: 2018-11-06
• Study First Posted: 2018-11-08
• Study Start: 2019-01-28
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-04
• Last Update Posted: 2024-06-05
• Primary Completion: 2026-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 45

Inclusion Criteria

Not provided

Exclusion Criteria

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
Progression-Free Survival (PFS)	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