Combining cryoablation with immunotherapy for advanced melanoma
A Phase II Study of Core Needle Biopsy and Cryoablation of an Enlarging Tumor in Patients With Advanced Melanoma Receiving Post-progression Dual Immune Checkpoint Inhibitor Therapy
This study is testing if freezing tumors along with two immunotherapy drugs can help people with advanced melanoma that hasn't improved with other treatments.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 37 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Massachusetts General Hospital Academic / other |
| Drugs / interventions | pembrolizumab, nivolumab, relatimab, atezolizumab, ipilimumab, radiation, prednisone, immunotherapy |
| Locations | 1 site (Boston, Massachusetts) |
| Trial ID | NCT05779423 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to evaluate the safety and effectiveness of combining cryoablation with two immunotherapy drugs, ipilimumab and nivolumab, for patients with unresectable metastatic melanoma that has not responded to previous PD-1 inhibitor treatments. The study is a single-arm, two-stage Phase II trial involving approximately 37 participants, who will undergo a series of procedures including tumor freezing, blood sample collections, and imaging scans. The goal is to determine if this combination can improve treatment outcomes for patients with resistant melanoma.
Who should consider this trial
Good fit: Ideal candidates are adults over 18 with unresectable metastatic melanoma who have progressed on prior immune checkpoint inhibitor therapy.
Not a fit: Patients with untreated or uncontrolled medical issues or those not eligible for dual checkpoint inhibition may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could provide a new treatment option for patients with advanced melanoma that is resistant to standard therapies.
How similar studies have performed: While the combination of cryoablation with immunotherapy is an innovative approach, similar studies have shown promise in enhancing treatment responses in resistant cancers.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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). * For participants with known evidence of known chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. (HBV testing not required at screening). * Participants with a history of known hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. (HCV testing not required at screening). * Participants with asymptomatic brain metastases are eligible. * Participants with new or progressive asymptomatic brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy. * Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * 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.
Where this trial is running
Boston, Massachusetts
- Massachusetts General Hospital Cancer Center — Boston, Massachusetts, United States (Recruiting)
Study contacts
- Principal investigator: Meghan J Mooradian, MD — Massachusetts General Hospital
- Study coordinator: Meghan J Mooradian, MD
- Email: mmooradian@mgh.harvard.edu
- Phone: 617-724-4000
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.