NCT04713371

A Phase 2 Trial for Patients With Metastatic Solid Cancer

A Phase 2 Trial of Cryosurgical Freezing and Multiplex Immunochemotherapy in Patients With Metastatic Solid Cancer

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Sponsor: Rampart Health, L.L.C. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study seeks to estimate the potential efficacy of the study treatment, as well as the occurrence of adverse events.

Detailed description

Cryosurgical freezing (limited to 1.5 cm diameter single freeze within the cancer (up to two cancer sites selected and treated)) will release intact antigens to prime the immune system. The study treatment immunotherapeutic drugs (PD-1 inhibitor monoclonal antibody nivolumab or pembrolizumab and anti-CTLA-4 monoclonal antibody ipilimumab, and low-dose cyclophosphamide) will then be sequentially injected directly into each of the treated cancer sites immediately following cryosurgical freezing. These injections will be performed in combination with collagen (Helitene) to improve drug containment at the site of injection for improved local effect rather than rapid disbursement and dilution throughout adjacent interstitial spaces, as well as sustained drug delivery over time rather than a burst-release pattern. Prior to study treatment, oral low dose cyclophosphamide will be given. Post-treatment, daily subcutaneous low-dose GM-CSF injections 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, low-dose cyclophosphamide, and metronomic GM-CSF. Intra-tumoral injection of the immunotherapeutic medications assists in stimulating and harnessing the local and systemic immune response. GM-CSF prolongs the immune response. Using this combination of therapies, referred to as AbscopalRx5001, it is thought that a clinically significant systemic anti-cancer immune response might be elicited. Intra-tumoral injection of drugs will likely offer fewer side effects than systemic therapy.

Conditions

• Metastatic Cancer

Interventions

Type	Name	Description
DRUG	Keytruda Injectable Product	Keytruda (pembrolizumab): PD-1 inhibitor antibody Injectable 50mg/mL, only 2 mL injected.
DRUG	Yervoy Injectable Product	Yervoy (ipilimumab): Anti-CTLA-4 antibody Injectable 5mg/mL, only 2 mL injected.
DRUG	Cytoxan	Injectable 250mg/m2, only 1 mL injected. Oral low dose cyclophosphamide: 50mg once daily pill for 5 days prior to first treatment, 3 days prior to 2nd and 3rd treatment.
PROCEDURE	Cryosurgical freezing (cryosurgery)	Cryosurgery, also known as cryoablation, for metastatic cancer works by freezing the cancer cells inside the tumor. Cryoablation will release intact antigens to prime the immune system.
DRUG	GM-CSF Injectable	Daily injection administered subcutaneously. 250 mcg daily injections for a total of 25 days post after each treatment.

Timeline

• Start date: 2021-05-19
• Primary completion: 2024-12-01
• Completion: 2024-12-01
• First posted: 2021-01-19
• Last updated: 2024-05-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study