NCT04090775

A Phase 2 Trial for Men With Metastatic Prostatic Adenocarcinoma

A Phase 2 Trial of Cryosurgical Freezing and Intratumoral Combination Immunotherapy in Men With Metastatic Prostatic Adenocarcinoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Rampart Health, L.L.C. · Industry
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study seeks to estimate the occurrence of adverse events related to the study treatment (Cryosurgical freezing and Intratumoral Combination Immunotherapy), as well as determine the potential efficacy.

Detailed description

Cryosurgical freezing will release intact antigens to prime the immune system. The study treatment immunotherapeutic drugs (PD-1 inhibitor monoclonal antibody nivolumab and anti-CTLA-4 monoclonal antibody ipilimumab, and cyclophosphamide) will then be sequentially injected directly into the cancer immediately following cryosurgical freezing. Oral low-dose cyclophosphamide will also be administered subsequently. It is speculated that neoantigens released from the cryoablated necrotic cancer will be available in the vicinity of the cryosurgical freezing field immediately following the procedure. Immature dendritic cells attracted to the injection site will internalize neoantigens to become activated to recognize cancer-specific antigenic proteins. The activated dendritic cells will recruit killer T-cells to the injection site to attack cancer cells, and then migrate through the lymphatic system to sites of metastases, targeting cancer-specific neoantigens and recruiting more killer T-lymphocytes to destroy other cancer cells harboring the precise antigenic epitopes (abscopal (bystander) effect). In this way, dendritic cells are capable of initiating cell-mediated systemic immune response in combination with cytotoxic killer T-cells. Regulatory T lymphocytes, which have been implicated in dampening or halting cell-mediated, antigen-specific immune responses, will be selectively depleted by anti-CTLA-4 monoclonal antibodies and low-dose cyclophosphamide. Intratumoral injection of the immunotherapeutic medications assists in stimulating and harnessing the local and systemic immune response. Oral cyclophosphamide prolongs the immune response. Using this combination of therapies, referred to as AbscopalRx1001, it is thought that a clinically significant systemic anti-cancer immune response might be elicited. Intratumoral injection of drugs will likely offer fewer side effects than systemic therapy.

Conditions

• Metastatic Prostatic Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Opdivo Injectable Product	Opdivo (nivolumab): PD-1 inhibitor antibody Injectable 10mg/mL, only 1 mL injected.
DRUG	Yervoy Injectable Product	Yervoy (ipilimumab): Anti-CTLA-4 antibody Injectable 5mg/mL, only 1 mL injected.
DRUG	Cytoxan	Cytoxan (cyclophosphamide): Chemotherapy agent Both Injectable and Oral low dose: Injectable 250mg/m2, only 1 mL injected. Oral low dose cyclophosphamide: option of either 50mg once daily pill or 25mg twice daily pill for two weeks on, then two weeks off, then two weeks on again.
PROCEDURE	Cryosurgical freezing (cryosurgery)	Cryosurgery, also known as cryoablation, for prostate cancer works by freezing the cancer cells inside the prostate gland. Cryoablation will release intact antigens to prime the immune system.

Timeline

• Start date: 2019-06-28
• Primary completion: 2020-07-30
• Completion: 2022-01-31
• First posted: 2019-09-16
• Last updated: 2022-06-21

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study