Clinical Trials/NCT03734692

NCT03734692

Active, Not Recruiting

Phase 1

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

Robert Edwards1 site in 1 country24 target enrollmentJanuary 28, 2019

ConditionsOvarian Cancer Recurrent

InterventionsRintatolimod Pembrolizumab Cisplatin

DrugsRintatolimod Pembrolizumab Cisplatin

Overview

Phase: Phase 1
Intervention: Rintatolimod
Conditions: Ovarian Cancer Recurrent
Sponsor: Robert Edwards
Enrollment: 24
Locations: 1
Primary Endpoint: Objective Response Rate (ORR)
Status: Active, Not Recruiting
Last Updated: 2 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

January 28, 2019

End Date

January 10, 2027

Last Updated

2 months ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

Robert Edwards

Responsible Party

Sponsor Investigator

Principal Investigator

Robert Edwards

Professor

University of Pittsburgh

Eligibility Criteria

Inclusion Criteria

•Patients must be at least 18 years of age on the day of signing informed consent.
•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 UPMC Cancer Centers if the patient did not have their initial surgery at Magee. Original tumor blocks may be reviewed after registration (informed consent and enrollment). Tumor block should be held until study is completed.
•Patients must have completed prior platinum-based therapy. Response can be complete or partial if it otherwise meets platinum sensitive criteria, see below.
•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 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.

Exclusion Criteria

•A WOCBP who has a positive urine pregnancy test within 72 hours prior to infusion of treatment regimen (see Appendix 3). 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 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-CNS disease.
•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-Guérin (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.
•o 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.

Arms & Interventions

cisplatin + rintatolimod + pembrolizumab

Intraperitoneal (IP) cisplatin 50mg/m\^2 solution with IP rintatolimod 200 mg solution and IV pembrolizumab 200 mg solution.

Intervention: Rintatolimod

cisplatin + rintatolimod + pembrolizumab

Intraperitoneal (IP) cisplatin 50mg/m\^2 solution with IP rintatolimod 200 mg solution and IV pembrolizumab 200 mg solution.

Intervention: Pembrolizumab

cisplatin + rintatolimod + pembrolizumab

Intraperitoneal (IP) cisplatin 50mg/m\^2 solution with IP rintatolimod 200 mg solution and IV pembrolizumab 200 mg solution.

Intervention: Cisplatin

Outcomes

Primary Outcomes

Objective Response Rate (ORR)

Time Frame: 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 Outcomes

DLTs Related to Treatment(At baseline (pre-treatment) and at 12 weeks (after the start of treatment))
Progression-Free Survival (PFS)(up to 4 years)
Time To Disease Progression(up to 4 years)
Change in CD4 Cells(At treatment Cycle 1 Day 3)
Change in CD4 Cells(At treatment Cycle 4 Day 1)
Change in CD4 Cells(At treatment Cycle 4 Day 3)
Percent of CD4 Cells(At treatment Cycle 1 Day 1)
Percent of CD4 Cells(At treatment Cycle 1 Day 3)
Percent of CD4 Cells(At treatment Cycle 4 Day 1)
Percent of CD4 Cells(At treatment Cycle 4 Day 3)
Change in CD8 Cells(At treatment Cycle 1 Day 3)
Change in CD8 Cells(At treatment Cycle 4 Day 1)
Change in CD8 Cells(At treatment Cycle 4 Day 3)
Percent of CD8 Cells(At treatment Cycle 1 Day 1)
Percent of CD8 Cells(At treatment Cycle 1 Day 3)
Percent of CD8 Cells(At treatment Cycle 4 Day 1)
Percent of CD8 Cells(At treatment Cycle 4 Day 3)
Change in CD14 Cells(At treatment Cycle 1 Day 3)
Change in CD14 Cells(At treatment Cycle 4 Day 1)
Change in CD14 Cells(At treatment Cycle 4 Day 3)
Percent of CD14 Cells(At treatment Cycle 1 Day 1)
Percent of CD14 Cells(At treatment Cycle 1 Day 3)
Percent of CD14 Cells(At treatment Cycle 4 Day 1)
Percent of CD14 Cells(At treatment Cycle 4 Day 3)
Change in CD19 Cells(At treatment Cycle 1 Day 3)
Change in CD19 Cells(At treatment Cycle 4 Day 1)
Change in CD19 Cells(At treatment Cycle 4 Day 3)
Percent of CD19 Cells(At treatment Cycle 1 Day 1)
Percent of CD19 Cells(At treatment Cycle 1 Day 3)
Percent of CD19 Cells(At treatment Cycle 4 Day 1)
Percent of CD19 Cells(At treatment Cycle 4 Day 3)
Change in CD56 Cells(At treatment Cycle 1 Day 3)
Change in CD56 Cells(At treatment Cycle 4 Day 1)
Change in CD56 Cells(At treatment Cycle 4 Day 3)
Percent of CD56 Cells(At treatment Cycle 1 Day 1)
Percent of CD56 Cells(At treatment Cycle 1 Day 3)
Percent of CD56 Cells(At treatment Cycle 4 Day 1)
Percent of CD56 Cells(At treatment Cycle 4 Day 3)
Overall Survival (OS)(Up to 3 years)
Change in CD3 Cells(At treatment Cycle 4 Day 1)
Change in CD3 Cells(At treatment Cycle 4 Day 3)
Percent of CD3 Cells(At treatment Cycle 1 Day 1)
Percent of CD3 Cells(At treatment Cycle 1 Day 3)
Percent of CD3 Cells(At treatment Cycle 4 Day 1)
Percent of CD3 Cells(At treatment Cycle 4 Day 3)
Change in CD45 Cells(At treatment Cycle 1 Day 3)
Change in CD45 Cells(At treatment Cycle 4 Day 1)
Change in CD45 Cells(At treatment Cycle 4 Day 3)
Percent of CD45 Cells(At treatment Cycle 1 Day 1)
Percent of CD45 Cells(At treatment Cycle 1 Day 3)
Percent of CD45 Cells(At treatment Cycle 4 Day 1)
Percent of CD45 Cells(At treatment Cycle 4 Day 3)
Change in CD3 Cells(At treatment Cycle 1 Day 3)