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

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.

Conditions

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

Interventions

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.

Sponsors & Collaborators

• Bristol-Myers Squibb

  collaborator INDUSTRY

• Children's National Research Institute

  lead OTHER

Principal Investigators

• AeRang Kim, MD, PhD · Children's National Research Institute

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Year

Max Age

39 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-02-18

Primary Completion

2024-03-12

Completion

2024-03-12

FDA Drug

Yes

Countries

• United States

Study Locations