Acral Lentiginous MelanomaPhase 2NCT02978443
A Biomarker Study in Advanced Mucosal or Acral Lentiginous Melanoma Receiving Nivolumab in Combination With Ipilimumab
A Phase 2 study testing Nivolumab and Ipilimumab in people with Acral Lentiginous Melanoma and Mucosal Melanoma, run by Georgetown University at 5 sites in United States.
Trial summary
Participants with advanced or metastatic mucosal melanoma (cohort A) and acral lentiginous melanoma (cohort B) eligible for treatment with nivolumab in combination with ipilimumab followed by nivolumab therapy will submit tissue blocks from tumors of malignant melanoma for histopathology review and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acral Lentiginous Melanoma, Mucosal Melanoma
- What is being tested?
- Nivolumab and Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 5 sitesUnited States
- Study dates
- 26 Jul 2017to 2 Aug 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients must have histologically confirmed MCM or ALM that is metastatic or unresectable.
- Patients must be eligible to receive nivolumab in combination with ipilimumab treatment per institutional guidelines.
- Patients must have a tissue block (or 20 unstained slides) available with adequate tumor to perform multiplex immunohistochemistry and nucleic acids analyses ( i.e. whole exome sequencing) Patients with only a previous fine-needle aspirate are ineligible for enrollment.
- Patients must be willing to donate a small amount of whole blood prior to treatment and during treatment for laboratory analysis.
- Patients must give informed consent prior to initiation of therapy.
- Patients must be ambulatory with good performance status (ECOG 0 or 1)
Who cannot join
- Patients who do not have available tissue for immunohistochemistry and nucleic acids analyses.
- Patients who have received prior immunotherapy for unresectable or metastatic disease.
- Patients with untreated brain metastases, leptomeningeal disease, or seizure disorders are ineligible. Patients with a history of brain metastases must have completed treatment (i.e. surgery or radiation) 1 month prior to enrollment and have no evidence of disease or edema on brain CT or head MRI.
- Patients with inadequate tissue for analysis.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
John Theurer Cacner Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007
Washington Cancer Institute at MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010
About this study
Official title: A Study to Estimate the Anti-Tumor Activity and Identify Potential Predictors of Response in Patients With Advanced Mucosal or Acral Lentiginous Melanoma Receiving Standard Nivolumab in Combination With Ipilimumab Followed by Nivolumab Monotherapy
Participants with advanced or metastatic mucosal melanoma (cohort A) and acral lentiginous melanoma (cohort B) eligible for treatment with nivolumab in combination with ipilimumab followed by nivolumab therapy will submit tissue blocks from tumors of malignant melanoma for histopathology review and immunohistochemistry analysis at Georgetown University-Lombardi Comprehensive Cancer Center. Pretreatment blood will be drawn and stored in the Melanoma Research Foundation Breakthrough Consortium Virtual Repository at each participating institution. At the end of participation, samples will be sent to Georgetown University-Lombardi Comprehensive Cancer Center for processing and storage. An optional pretreatment biopsy of an accessible tumor lesion will be performed in a subset of enrolled patients. Patients will receive nivolumab in combination with ipilimumab according to the standard FDA approved treatment regimen.
Read the detailed description
Immunotherapy with HD-IL-2 has produced durable benefit in 10% of patients with metastatic cutaneous melanoma. The antitumor activity of IL-2 has been limited at least in part by immunosuppressive and immune-regulatory forces within the tumor microenvironment. Antibodies against CTLA4 (e.g. ipilimumab), PD1 and its ligand (PD-L1) produced long-term benefit in approximately 20-40% of patients with advanced melanoma. In addition, the combination of ipilimumab with the anti-PD1 antibody, nivolumab, has shown tumor responses in up to 60% of patients with advanced melanoma. These findings have led to FDA approval of ipilimumab and nivolumab as an indication for treatment of patients with advanced melanoma and nivolumab for other cancers. While these data are exciting, only a few patients enrolled to the prior studies had metastatic MCM or ALM. There is no prospective immunotherapy studies conducted in MCM or ALM-specific population. Therefore the activity of the ipilimumab + nivolumab combination in these subsets or patients remains unknown
Reliable predictive biomarkers for the use of immune checkpoint inhibitors are needed to identify pretreatment those patients most likely to respond and early on in treatment assays could help identify mechanisms of tumor response and resistance necessary to improve therapy. Although tumor PD-L1 expression in tumor confers higher treatment response rate, responses to nivolumab or nivolumab + ipilimumab alone were noted in 55% and 41% of patients, respectively, with PD-L1- tumors. Therefore, more reliable predictive biomarkers are needed.
Recently, extensive studies on metastatic colorectal cancer have demonstrated that a new scoring system as well as density of immune cells infiltrates at the center of the tumor and its invasive margin, described as Immunoscore, could accurately separate a group of patients with high Immunoscore with improved DFS, and OS from those with low Immunoscore where the histopathological staging system cannot. A recent study has also demonstrated relationship between degree of pre-treatment CD8+ tumor infiltrating lymphocytes (TILs) infiltration and PD-L1 expression at the invasive margin of the advanced cutaneous melanoma and improved long-term clinical benefits in patients with advanced melanoma who received pembrolizumab monotherapy. Further, there appeared to be an association between tumor response and clonality of the immune infiltrate based on a next-generation sequencing method used to evaluate T-cell receptor rearrangement pre- and in response to checkpoint inhibitor therapy. Also, high mutational burden correlated with overall survival in patients with cutaneous melanoma treated with ipilimumab or lung cancer treated with anti-PD1. However, the biology of MCM and ALM are distinct from cutaneous melanoma at multiple levels. Consequently, the utility of predictive biomarkers developed for cutaneous melanoma remains unknown.
- Conditions
- Acral Lentiginous Melanoma, Mucosal Melanoma
- Being tested
- Nivolumab, Ipilimumab
- Keywords
- Melanoma, Mucosal, Acral Lentiginous, Ipilimumab, Nivolumab, Anti-tumor, Potential Predictors, Opdivo, Yervoy
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called BMS-936558, Opdivo
nivolumab administered IV over 60 minutes at 1 mg/kg every 3 weeks for 4 treatment cycles (Induction) then continue with nivolumab administered IV over 60 minutes at 3 mg/kg every 2 weeks
IpilimumabDrug
Also called BMS-734016, Yervoy
ipilimumab administered IV over 90 minutes at 3 mg/kg every 3 weeks for 4 treatment cycles (Induction)
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab-Ipilimumab Combination Therapy | Experimental | All patients will receive nivolumab administered IV over 60 minutes at 1 mg/kg combined with ipilimumab administered IV over 90 minutes at 3 mg/kg every 3 weeks for 4 treatment cycles (Induction) then continue with nivolumab administered IV over 60 minutes at 3 mg/kg every 2 weeks until progression, intolerable toxicity, or a maximum of 48 weeks, whichever comes first (Maintenance). Patients exhibiting complete response (CR) should continue nivolumab monotherapy at least 12 weeks beyond documentation of CR, if possible. Receives: Drug: Nivolumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) With Mucosal Melanoma (MCM)
ORR, defined as complete response [CR] + partial response [PR] per RECIST 1.1 criteria and to compare this response rate to the response rate of patients with "good" molecular predictive features
Measured: 24 months
Secondary outcomes (3)
Objective Response Rate With Acral Lentiginous Melanoma (ALM)
ORR, defined as complete response [CR] + partial response [PR] per RECIST 1.1 criteria and to compare this response rate to the response rate of patients with "good" molecular predictive features
Measured: 24 months
Progression-free Survival (PFS)
Progression-free survival is defined as the time from the date of treatment initiation until the date that disease progression criteria are met or the date death without progression, or is censored at the date of last disease assessment without evidence of progression.
Measured: 33 months
Overall Survival (OS)
OS is calculated from the date of treatment initiation to the date of death, or censored at date of last contact.
Measured: 44 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2016 (estimated)
- Study start26 Jul 2017
- Primary completion28 Jul 2020
- Study completion2 Aug 2022
Why it stopped: Lack of Enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acral Lentiginous MelanomaStudies of the same condition, open and under way.
- More trials run by Georgetown UniversityThe 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
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Georgetown University
- Sponsor type
- University, hospital or other
- Collaborators
- Melanoma Research Foundation Breakthrough Consortium, Bristol-Myers Squibb, University of Colorado, Denver, University of California, San Francisco, Vanderbilt University, Columbia University, University of Pittsburgh, Yale University, M.D. Anderson Cancer Center, H. Lee Moffitt Cancer Center and Research Institute, Memorial Sloan Kettering Cancer Center, Northwestern University, Dana-Farber Cancer Institute
- Responsible party
- Sponsor
- Investigators
- Suthee Rapisuwon, MD, Study chair, Lombardi Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02978443
- Sponsor's protocol ID
- 2016-0420
- Other IDs
- CA209-763
- Status last verified
- Mar 2024
- First submitted
- 23 Nov 2016
- Last updated
- 4 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Estimate the Anti-Tumor Activity and Identify Potential Predictors of Response in Patients With Advanced Mucosal or Acral Lentiginous Melanoma Receiving Standard Nivolumab in Combination With Ipilimumab Followed by Nivolumab Monotherapy
- ClinicalTrials.gov ID
- NCT02978443
- Acronym / sponsor ID
- 2016-0420
- Conditions
- Acral Lentiginous Melanoma, Mucosal Melanoma
- Keywords
- Melanoma, Mucosal, Acral Lentiginous, Ipilimumab, Nivolumab, Anti-tumor, Potential Predictors, Opdivo
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of Enrollment
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Georgetown UniversityUniversity, hospital or other
- Collaborators
- Melanoma Research Foundation Breakthrough Consortium, Bristol-Myers Squibb, University of Colorado, Denver, University of California, San Francisco, Vanderbilt University, Columbia University, University of Pittsburgh, Yale University, M.D. Anderson Cancer Center, H. Lee Moffitt Cancer Center and Research Institute, Memorial Sloan Kettering Cancer Center, Northwestern University, Dana-Farber Cancer Institute
- Study start
- 26 Jul 2017 (actual)
- Primary completion
- 28 Jul 2020 (actual)
- Study completion
- 2 Aug 2022 (actual)
- First posted
- 1 Dec 2016 (estimated)
- Results
- Posted 4 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Participants with advanced or metastatic mucosal melanoma (cohort A) and acral lentiginous melanoma (cohort B) eligible for treatment with nivolumab in combination with ipilimumab followed by nivolumab therapy will submit tissue blocks from tumors of malignant melanoma for histopathology review and immunohistochemistry analysis at Georgetown University-Lombardi Comprehensive Cancer Center. Pretreatment blood will be drawn and stored in the Melanoma Research Foundation Breakthrough Consortium Virtual Repository at each participating institution. At the end of participation, samples will be sent to Georgetown University-Lombardi Comprehensive Cancer Center for processing and storage. An optional pretreatment biopsy of an accessible tumor lesion will be performed in a subset of enrolled patients. Patients will receive nivolumab in combination with ipilimumab according to the standard FDA approved treatment regimen.
Detailed description
Immunotherapy with HD-IL-2 has produced durable benefit in 10% of patients with metastatic cutaneous melanoma. The antitumor activity of IL-2 has been limited at least in part by immunosuppressive and immune-regulatory forces within the tumor microenvironment. Antibodies against CTLA4 (e.g. ipilimumab), PD1 and its ligand (PD-L1) produced long-term benefit in approximately 20-40% of patients with advanced melanoma. In addition, the combination of ipilimumab with the anti-PD1 antibody, nivolumab, has shown tumor responses in up to 60% of patients with advanced melanoma. These findings have led to FDA approval of ipilimumab and nivolumab as an indication for treatment of patients with advanced melanoma and nivolumab for other cancers. While these data are exciting, only a few patients enrolled to the prior studies had metastatic MCM or ALM. There is no prospective immunotherapy studies conducted in MCM or ALM-specific population. Therefore the activity of the ipilimumab + nivolumab combination in these subsets or patients remains unknown
Reliable predictive biomarkers for the use of immune checkpoint inhibitors are needed to identify pretreatment those patients most likely to respond and early on in treatment assays could help identify mechanisms of tumor response and resistance necessary to improve therapy. Although tumor PD-L1 expression in tumor confers higher treatment response rate, responses to nivolumab or nivolumab + ipilimumab alone were noted in 55% and 41% of patients, respectively, with PD-L1- tumors. Therefore, more reliable predictive biomarkers are needed.
Recently, extensive studies on metastatic colorectal cancer have demonstrated that a new scoring system as well as density of immune cells infiltrates at the center of the tumor and its invasive margin, described as Immunoscore, could accurately separate a group of patients with high Immunoscore with improved DFS, and OS from those with low Immunoscore where the histopathological staging system cannot. A recent study has also demonstrated relationship between degree of pre-treatment CD8+ tumor infiltrating lymphocytes (TILs) infiltration and PD-L1 expression at the invasive margin of the advanced cutaneous melanoma and improved long-term clinical benefits in patients with advanced melanoma who received pembrolizumab monotherapy. Further, there appeared to be an association between tumor response and clonality of the immune infiltrate based on a next-generation sequencing method used to evaluate T-cell receptor rearrangement pre- and in response to checkpoint inhibitor therapy. Also, high mutational burden correlated with overall survival in patients with cutaneous melanoma treated with ipilimumab or lung cancer treated with anti-PD1. However, the biology of MCM and ALM are distinct from cutaneous melanoma at multiple levels. Consequently, the utility of predictive biomarkers developed for cutaneous melanoma remains unknown.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nivolumab-Ipilimumab Combination Therapy | Experimental | Drug: Nivolumab, Drug: IpilimumabAll patients will receive nivolumab administered IV over 60 minutes at 1 mg/kg combined with ipilimumab administered IV over 90 minutes at 3 mg/kg every 3 weeks for 4 treatment cycles (Induction) then continue with nivolumab administered IV over 60 minutes at 3 mg/kg every 2 weeks until progression, intolerable toxicity, or a maximum of 48 weeks, whichever comes first (Maintenance). Patients exhibiting complete response (CR) should continue nivolumab monotherapy at least 12 weeks beyond documentation of CR, if possible. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must have histologically confirmed MCM or ALM that is metastatic or unresectable.
- Patients must be eligible to receive nivolumab in combination with ipilimumab treatment per institutional guidelines.
- Patients must have a tissue block (or 20 unstained slides) available with adequate tumor to perform multiplex immunohistochemistry and nucleic acids analyses ( i.e. whole exome sequencing) Patients with only a previous fine-needle aspirate are ineligible for enrollment.
- Patients must be willing to donate a small amount of whole blood prior to treatment and during treatment for laboratory analysis.
- Patients must give informed consent prior to initiation of therapy.
Key exclusion criteria (4 listed)
- Patients who do not have available tissue for immunohistochemistry and nucleic acids analyses.
- Patients who have received prior immunotherapy for unresectable or metastatic disease.
- Patients with untreated brain metastases, leptomeningeal disease, or seizure disorders are ineligible. Patients with a history of brain metastases must have completed treatment (i.e. surgery or radiation) 1 month prior to enrollment and have no evidence of disease or edema on brain CT or head MRI.
- Patients with inadequate tissue for analysis.
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 |
|---|---|---|
| NivolumabAlso: BMS-936558, Opdivonivolumab administered IV over 60 minutes at 1 mg/kg every 3 weeks for 4 treatment cycles (Induction) then continue with nivolumab administered IV over 60 minutes at 3 mg/kg every 2 weeks | Drug | Nivolumab-Ipilimumab Combination Therapy |
| IpilimumabAlso: BMS-734016, Yervoyipilimumab administered IV over 90 minutes at 3 mg/kg every 3 weeks for 4 treatment cycles (Induction) | Drug | Nivolumab-Ipilimumab Combination Therapy |
Primary outcome
Objective Response Rate (ORR) With Mucosal Melanoma (MCM)
Time frame: 24 months
ORR, defined as complete response [CR] + partial response [PR] per RECIST 1.1 criteria and to compare this response rate to the response rate of patients with "good" molecular predictive features
3 secondary outcomes
Objective Response Rate With Acral Lentiginous Melanoma (ALM)
Time frame: 24 months
Progression-free Survival (PFS)
Time frame: 33 months
Overall Survival (OS)
Time frame: 44 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Using Biomarkers to Help Guide Safe Immunotherapy Discontinuation in Patients With Unresectable Stage IIIB-IV Melanoma, The PET-Stop Trial
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A Study to Compare the Administration of Encorafenib + Binimetinib + Nivolumab Versus Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases
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Dinaciclib in Treating Patients With Stage IV Melanoma
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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. This study is not recruiting at the moment.
Suthee Rapisuwon, MD study chair
Lombardi Comprehensive Cancer Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab and Ipilimumab in people with Acral Lentiginous Melanoma and Mucosal Melanoma, run by Georgetown University at 5 sites 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 6 inclusion and 4 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: stopped early, as of the sponsor's last update on 4 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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?
Yes. Results are posted in the registry (first posted 4 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) With Mucosal Melanoma (MCM) (time frame: 24 months). 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 4 Apr 2024; AzTrials last refreshed its copy on 7 Nov 2026.