Metastatic MelanomaPhase 2NCT05779423
Cryoablation+Ipilimumab+Nivolumab in Melanoma
A Phase 2 study testing Ipilimumab, Nivolumab and Cryoablation in people with Metastatic Melanoma and Skin Cancer, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma, Skin Cancer
- What is being tested?
- Ipilimumab, Nivolumab and Cryoablation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Sep 2023to 1 Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 21Show fewer
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Meghan J Mooradian, MD, 617-724-4000, mmooradian@mgh.harvard.edu
Meghan J Mooradian, MD
About this study
Official title: 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
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)
Read the detailed description
This is a single-arm, two-stage, Phase II clinical trial to test the safety and effectiveness of an investigational treatment, the combination of ipilimumab and nivolumab with cryoablation, for the treatment of metastatic melanoma resistant to PD-1 inhibition.
Ipilimumab and nivolumab are types of inhibitors. Ipilimumab targets and blocks specific proteins in cancer cells which are responsible for stopping the immune system from working correctly. Nivolumab targets a receptor on cancer cells that causes programmed cell death.
The U.S. Food and Drug Administration has approved Ipilimumab and Nivolumab for the treatment of melanoma.
Cryoablation is an approved procedure that consists of freezing a tumor and surgically removing it. The use of the study drugs and cryoablation combination is experimental.
Study procedures including screening for eligibility, study treatment including in-clinic visits, blood sample collections, Computerized Tomography (CT) scans, and tumor biopsies.
Participation in this research study is expected to last up to 3 years.
It is expected that about 37 people will take part in this research study.
The William M. Wood Foundation is supporting this research by providing funding for the cryoablation and research activities.
- Conditions
- Metastatic Melanoma, Skin Cancer
- Being tested
- Ipilimumab, Nivolumab, Cryoablation
- Keywords
- Immunotherapy, Metastatic Melanoma, Resistant Metastatic Melanoma, Skin Cancer, Cryoablation
- Medical subject headings
- Melanoma, Skin Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
Also called Yervoy
Monoclonal antibody administered through intravenous infusion
NivolumabDrug
Also called Opdivo
Monoclonal antibody administered through intravenous infusion
CryoablationProcedure or surgery
Procedure of freezing a tumor performed via CT-guidance by interventional radiologist.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ipilimumab; Drug: Nivolumab; Procedure: Cryoablation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months post-1st cryoablation
Secondary outcomes (4)
Number of Participants with Adverse Events
Defined as all adverse events (grade 1- 5) occurring during the trial and follow-up period will be summarized using CTCAE v5.0 and the Kaplan-Meier method.
Measured: Baseline to 3 months post-cryoablation
Duration of Overall Response
Defined as the time interval between the first declaration of response/stable disease and date of disease progression per RECIST v1.1 criteria and summarized using the Kaplan-Meier method.
Measured: 6 months post-1st cryoablation
Progression-Free Survival (PFS)
Defined as the time interval between study enrollment and documented progression of disease per RECIST v1.1 criteria and summarized using the Kaplan-Meier method.
Measured: 6 months post-1st cryoablation
Overall Survival (OS)
Assessed per RECIST 1.1 criteria.
Measured: 6 months post-1st cryoablation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2023
- Study start23 Sep 2023
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Meghan Mooradian, Massachusetts General Hospital
- Investigators
- Meghan J Mooradian, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05779423
- Sponsor's protocol ID
- 22-619
- Status last verified
- Aug 2026
- First submitted
- 9 Mar 2023
- Last updated
- 27 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05779423
- Acronym / sponsor ID
- 22-619
- Conditions
- Metastatic Melanoma, Skin Cancer
- Keywords
- Immunotherapy, Metastatic Melanoma, Resistant Metastatic Melanoma, Skin Cancer, Cryoablation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 23 Sep 2023 (actual)
- Primary completion
- 1 Jan 2028 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 22 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Detailed description
This is a single-arm, two-stage, Phase II clinical trial to test the safety and effectiveness of an investigational treatment, the combination of ipilimumab and nivolumab with cryoablation, for the treatment of metastatic melanoma resistant to PD-1 inhibition.
Ipilimumab and nivolumab are types of inhibitors. Ipilimumab targets and blocks specific proteins in cancer cells which are responsible for stopping the immune system from working correctly. Nivolumab targets a receptor on cancer cells that causes programmed cell death.
The U.S. Food and Drug Administration has approved Ipilimumab and Nivolumab for the treatment of melanoma.
Cryoablation is an approved procedure that consists of freezing a tumor and surgically removing it. The use of the study drugs and cryoablation combination is experimental.
Study procedures including screening for eligibility, study treatment including in-clinic visits, blood sample collections, Computerized Tomography (CT) scans, and tumor biopsies.
Participation in this research study is expected to last up to 3 years.
It is expected that about 37 people will take part in this research study.
The William M. Wood Foundation is supporting this research by providing funding for the cryoablation and research activities.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ipilimumab + Nivolumab + Cryoablation | Experimental | Drug: Ipilimumab, Drug: Nivolumab, Procedure: CryoablationStudy 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IpilimumabAlso: YervoyMonoclonal antibody administered through intravenous infusion | Drug | Ipilimumab + Nivolumab + Cryoablation |
| NivolumabAlso: OpdivoMonoclonal antibody administered through intravenous infusion | Drug | Ipilimumab + Nivolumab + Cryoablation |
| CryoablationProcedure of freezing a tumor performed via CT-guidance by interventional radiologist. | Procedure or surgery | Ipilimumab + Nivolumab + Cryoablation |
Primary outcome
Rate of Clinical Benefit
Time frame: 6 months post-1st cryoablation
Defined as the proportion of participants with best overall response per RECIST v1.1 of confirmed complete or partial response or stable disease.
4 secondary outcomes
Number of Participants with Adverse Events
Time frame: Baseline to 3 months post-cryoablation
Duration of Overall Response
Time frame: 6 months post-1st cryoablation
Progression-Free Survival (PFS)
Time frame: 6 months post-1st cryoablation
Overall Survival (OS)
Time frame: 6 months post-1st cryoablation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2026.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Related trials for Metastatic Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
RecruitingPhase 3
A Study With Combinations of Anti-LAG-3 and Anti-PD-1 Antibodies in Adult Participants With Advanced or Metastatic Melanoma (Harmony Head-to-Head)
Melanoma
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 1/2
A Study of ST-1898 for Unresectable or Metastatic Melanoma
Unresectable or Metastatic Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Meghan J Mooradian, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ipilimumab, Nivolumab and Cryoablation in people with Metastatic Melanoma and Skin Cancer, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Meghan J Mooradian, MD (617-724-4000, mmooradian@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Clinical Benefit (time frame: 6 months post-1st cryoablation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.