Cryoablation+Ipilimumab+Nivolumab in Melanoma

NCT05779423 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-619
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to find out whether the combination of two approved drugs, ipilimumab and nivolumab, in combination with cryoablation are safe and effective for participants who have an unresectable melanoma that is resistant, or is growing, after receiving immunotherapy with a PD-1 inhibitor. The names of the study interventions involved in this study are:

• Cryoablation (an interventional radiology procedure that freezes part of a tumor)
• Ipilimumab (an immunotherapy)
• Nivolumab (an immunotherapy)

Conditions

Metastatic Melanoma; Skin Cancer

Keywords

Immunotherapy; Metastatic Melanoma; Resistant Metastatic Melanoma; Skin Cancer; Cryoablation

Outcome Measures

Primary Outcomes (1)

• Rate of Clinical Benefit

  Defined as the proportion of participants with best overall response per RECIST v1.1 of confirmed complete or partial response or stable disease.

  6 months post-1st cryoablation

Secondary Outcomes (4)

• Number of Participants with Adverse Events

  Baseline to 3 months post-cryoablation

• Duration of Overall Response

  6 months post-1st cryoablation

• Progression-Free Survival (PFS)

  6 months post-1st cryoablation

• Overall Survival (OS)

  6 months post-1st cryoablation

Study Arms (1)

Ipilimumab + Nivolumab + Cryoablation

EXPERIMENTAL

Study will be conducted in two stages: Stage 1: Will enroll 15 participants, and if 6 or more have clinical benefit, the study will proceed to Stage 2. * Baseline CT scan. * Cycle 1-4: Pre-determined doses of ipilimumab and nivolumab. Medications administered under direction of treating oncologist. * Day 2 - 14: Core Needle Biopsy followed by cryoablation between Cycle 1 - 2 * Surveillance CT scan at weeks 8 - 12, weeks 16 - 24. * Follow up for 6 months to assess safety after cryoablation. Participants followed for duration of response. Stage 2: Will enroll 22 participants * Baseline CT scan. * Cycle 1-4: Pre-determined doses of ipilimumab and nivolumab. Medications administered under direction of treating oncologist. * Day 2- 14: Core Needle Biopsy followed by cryoablation between Cycle 1 - 2. * Surveillance CT scan at weeks 8 - 12, weeks 16 - 24 * Follow up period to assess safety 6 months after cryoablation. Patients followed for duration of response.

Drug: Ipilimumab; Drug: Nivolumab; Procedure: Cryoablation

Interventions

Ipilimumab DRUG

Monoclonal antibody administered through intravenous infusion

Also known as: Yervoy

Ipilimumab + Nivolumab + Cryoablation

Nivolumab DRUG

Monoclonal antibody administered through intravenous infusion

Also known as: Opdivo

Ipilimumab + Nivolumab + Cryoablation

Cryoablation PROCEDURE

Procedure of freezing a tumor performed via CT-guidance by interventional radiologist.

Ipilimumab + Nivolumab + Cryoablation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (age \> 18) with unresectable melanoma who have progressed on immune checkpoint inhibitor therapy (pembrolizumab, nivolumab, nivolumab-relatimab, atezolizumab, ipilimumab) and for whom their treating physician plans to initiate dual ICI with ipilimumab and nivolumab. Progression on adjuvant PD-1 inhibition is permitted. PD-1 does not have to be the last therapy received. This is no limited on prior lines of ICI received. There is no wash-out period required from the time of their last therapy.
• Patients are medically eligible for dual checkpoint inhibition (i.e. no untreated/uncontrolled intercurrent medical issue including ongoing immune-related adverse event or need for systemic steroids \>10mg PO prednisone or its equivalent, ECOG PS ≤2) with ipilimumab 3mg/kg and nivolumab 1mg/kg by their treating physician
• Must have a tumor amenable to percutaneous image-guided cryoablation based on routine Interventional Radiology criteria.
• Patients must have measurable disease (by RECIST) independent of the lesion to be ablated. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 11 (Measurement of Effect) for evaluation of measurable disease.
• Prior radiation therapy to any site is allowed; with an exception of the target site for planned cryoablation
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Life expectancy of greater than 3 months
• Participants must have adequate organ and marrow function as defined below:
• Leukocytes ≥3,000/mcL
• Absolute neutrophil count ≥1,000/mcL
• Platelets ≥75,000/mcL
• Total bilirubin ≤3 institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤5 × institutional ULN
• CrCL \> 30 ml/min
• Known Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. (HIV testing not required at screening).

You may not qualify if:

• Lesion to undergo cryoablation cannot have had prior radiation therapy or other locoregional therapy
• Inability to hold systemic anticoagulation prior to cryoablation (if holding anticoagulation is required by the operator)
• Participants who are receiving an investigational agent(s).
• Participants who are progressing on combination ipilimumab/nivolumab as their last line of therapy
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1)
• Patients with symptomatic brain metastasis or LMD
• Participants on \> 10mg of oral prednisone or its equivalent
• Participants with uncontrolled intercurrent illness.
• Pregnant women are excluded from this study because immune checkpoint inhibitors have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with immune checkpoint inhibitors, breastfeeding should be discontinued.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

Ipilimumab; Nivolumab; Cryosurgery

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Meghan J Mooradian, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meghan J Mooradian, MD

CONTACT

617-724-4000; mmooradian@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 9, 2023
• First Posted: March 22, 2023
• Study Start: September 23, 2023
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: January 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)