NCT05302921

Neoadjuvant Dual Checkpoint Inhibition and Cryoablation in Relapsed/Refractory Pediatric Solid Tumors

Phase II Study Investigating the Efficacy of Neoadjuvant Dual Checkpoint Inhibition and Cryoablation Therapy in Children, Adolescents, and Young Adults With Relapsed/Refractory Solid Tumors

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: Children's National Research Institute · Academic / Other
• Sex: All
• Age: 1 Year – 39 Years
• Healthy volunteers: Not accepted

Summary

The is a phase II, single arm, open-label, multi-site trial studying the combination of cryoablation therapy and dual checkpoint inhibition with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) given at the recommended phase 2 dose (RP2D) in pediatric and young adult patients with relapsed or refractory solid tumors.

Detailed description

Patients less than 40 years old with relapsed/refractory solid tumors and at least two sites of measurable disease will receive the current pediatric RP2D of nivolumab and ipilimumab for one cycle and undergo cryoablation therapy of one tumor site. Patients will continue to receive cycles of checkpoint inhibition as long as there is no disease progression of unacceptable toxicity (maximum of 13 cycles \[12 months\]).

Conditions

• Osteosarcoma
• Ewing Sarcoma
• Rhabdomyosarcoma
• Relapsed Pediatric Solid Tumor
• Refractory Pediatric Solid Tumor
• Melanoma
• Hepatoblastoma
• Hepatocellular Carcinoma
• Neuroblastoma
• Wilms Tumor

Interventions

Type	Name	Description
PROCEDURE	Cryoablation Therapy	Cryoablation therapy is an established method of cancer treatment in adults and pediatrics with certain types of tumors and is standard of care for certain tumors in the setting of progression/relapse. Percutaneous image-guided Cryoablation (cryosurgery, cryotherapy) is a technique that utilizes successive rapid freeze/thaw cycles to destroy tumor cells. This technique is performed by inserting specialized needles known as cryoprobes into target tumors under imaging guidance with Computed Tomography (CT) and Ultrasound (US), or Magnetic Resonance Imaging (MRI). After the cryoprobe needles are placed within the target tumor, rapid cooling of liquid gas inserted into these probes leads to temperatures reaching -20 to -40 degrees Celsius. Cryoablation therapy of one disease site will be done starting Day 3 and prior to Day 15 of Cycle 1 only.
DRUG	Nivolumab	Nivolumab (Bristol Myers Squibb) is a human monoclonal antibody (immunoglobulin G4) that targets the programmed death-1 cluster of differentiation 279 (CD279) cell surface membrane receptor. Nivolumab and ipilimumab will be given on day 1 of 21-day cycles for cycles 1-4, followed by nivolumab alone on days 1 and 15 of 28-day cycles for cycles 5+. Patients will receive up to 13 cycles of therapy unless unacceptable toxicity or progression of disease.
DRUG	Ipilimumab	Ipilimumab (Bristol Myers Squibb) is a fully human monoclonal immunoglobulin G1Κ specific for human cytotoxic T-lymphocyte antigen 4 (CTLA-4, cluster of differentiation \[CD\]152), which is expressed on a subset of activated T-cells. Nivolumab and ipilimumab will be given on day 1 of 21-day cycles for cycles 1-4, followed by nivolumab alone on days 1 and 15 of 28-day cycles for cycles 5+. Patients will receive up to 13 cycles of therapy unless unacceptable toxicity or progression of disease.

Timeline

• Start date: 2022-02-18
• Primary completion: 2024-03-12
• Completion: 2024-03-12
• First posted: 2022-03-31
• Last updated: 2025-01-01

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study