A Phase 2 Efficacy Trial of Intensive Locoregional Chemoimmunotherapy, Intradermal Autologous Alpha-DC1 Vaccines, and Systemic Pembrolizumab for Advanced-Stage Ovarian Cancer
Kalinski, Pawel, MD, PhD
Summary
This trial proposes to evaluate the immunologic and potential clinical effectiveness of intensive locoregional sequential intraperitoneal (IP) cisplatin (IPC) with intravenous (iv) paclitaxel followed by peritoneal infusion of a chemokine modulatory (CKM) regimen composed of a cocktail of IP rintatolimod and interferon-alpha (IFNα) for patients with advanced stage ovarian cancer (III-IV) in the primary neoadjuvant setting. It was previously determined the tolerable dose of IPC-CKM. This study will add intradermal (ID) autologous αDC1 vaccines (known to be nontoxic) to the tolerable IPC-CKM regimen and systemic Keytruda (pembrolizumab). To optimize the pattern of immunity, all patients will also receive oral celecoxib (COX2 inhibitor).
Description
In addition to its typically late detection, the difficulty in treating OvCa results from its particular adeptness at avoiding immune elimination. Several vaccine trials targeting ovarian cancer have recently reported a lack of efficacy with vaccine only approaches. OvCa cells have been reported to display numerous defects in their MHC class I antigen-presenting capacity, involving loss of HLA alleles and loss of the molecules involved in the generation of antigenic peptides. In addition to these passive mechanisms of immune subversion, OvCa employs a series of active suppressive mechanisms, i…
Eligibility
- Age range
- 18+ years
- Sex
- Female
- Healthy volunteers
- No
Inclusion Criteria: 1. Patients must have advanced stage (III-IV) epithelial carcinoma or carcinosarcoma of ovarian, tubal or peritoneal origin. a. Histologic documentation of the original primary tumor is required via a pathology report. 2. Patients must be eligible for cancer-related definitive therapy with neoadjuvant chemotherapy. 3. Patients must be chemo-naive and receiving therapy in primary first-line neoadjuvant setting. 4. Patients must have ECOG performance of 0-1. 5. Patients must be reasonable candidate for interval debulking surgery as well as for IP platinum-based combinati…
Interventions
- DrugPaclitaxel
A chemotherapy for cancer patients that interferes structures that help move chromosomes during cell division, thus stabilizing these structures to prevents cancer cells from dividing and ultimately causing them to die. Dose: 175 mg/m\^2 IV on D1 each cycle during neoadjuvant and adjuvant periods.
- DrugCisplatin
An alkylating agent that contains platinum, which binds to DNA in cancer cells, causing cross-links that prevent DNA replication and repair, leading to cell death, particularly in rapidly dividing cancer cells. Dose: 75 mg/m\^2 IP / 1 hour on D1 of each cycle during neoadjuvant and adjuvant treatment periods.
- DrugBioferon
Inhibits replication of a wide range of RNA and DNA viruses and exerts antiproliferative effects on malignant cells. It suppresses antibody formation through an effect on B-lymphocytes and inhibits onset of delayed hypersensitivity. Dose:6 milli on units/100 mL IP over 30-60 minutes on D2 of each cycle during neoadjuvant and adjuvant treatment. D1 during maintenance treatment periods.
- DrugRintatolimod
A synthetic double-stranded RNA that selectively activates Toll-like Receptor 3 (TLR3), triggering antiviral and immunomodulatory responses, priming the immune system without causing excessive inflammation. Dose: 200 mg IP over 1-2 hours on D2 of each cycle during the neoadjuvant and adjuvant treatment periods. D1 during maintenance treatment periods
Location
- UMPC Hillman Cancer CenterPittsburgh, Pennsylvania