MelanomaPhase 2NCT04091750
Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma
A Phase 2 study testing Nivolumab, Ipilimumab and Cabozantinib in people with Melanoma, run by Georgetown University at 3 sites in United States.
Trial summary
In this phase II advanced melanoma study, all patients will receive treatment with nivolumab/ipilimumab plus cabozantinib for a 12 week induction period followed by nivolumab plus cabozantinib maintanence to complete up to 2 years of therapy unless disease progression, dose limiting toxicity, provider/patient decision… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Nivolumab, Ipilimumab and Cabozantinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 3 sitesUnited States
- Study dates
- 2 Mar 2020to Dec 2026
- 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
- All patients must have unresectable stage IIIb-IIId or IV melanoma by AJCC 8th edition. Note: Patients with uveal melanoma are excluded from this study.
- Age > 18 and ECOG Performance Status of 0 or 1.
- Measurable disease by RECIST 1.1
- Baseline tumor specimen available.
- Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
- Adequate organ and marrow function.
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- Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
- Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment.
- Female subjects of childbearing potential must not be pregnant at screening.
Who cannot join
- Prior treatment with anti-PD-1/PD-L1 therapy, anti-CTLA-4 therapy or cabozantinib. Prior adjuvant anti-PD-1 and/or anti-CTLA-4 therapy is allowed if relapse is greater than 6 months from last dose.
- Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
- Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
- Radiation therapy for bone metastasis or brain metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment.
- Known brain metastases that are >10mm or cranial epidural disease unless adequately treated with radiosurgery and/or surgery (including radiosurgery). Eligible subjects must be neurologically asymptomatic and without corticosteroid requirement. Dexamethasone < 2mg daily (or equivalent) will be allowed if discontinuation of corticosteroids is not feasible due to post-radiation effects and patient is asymptomatic. Patients with active, asymptomatic brain metastases that are <10mm and no corticosteroid requirement will be allowed without radiosurgery or surgery.
- History of active autoimmune disorder requiring immunosuppressive agents. Patients with autoimmune disorders considered low risk, such as vitiligo and thyroiditis, will be allowed.
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- Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g. dabigatran), betrixaban, or platelet inhibitors (eg, clopidogrel).
- Allowed anticoagulants are the following:
- Prophylactic use of Low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH) are permitted.
- Anticoagulation with therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban is allowed in subjects without known brain metastases who are on a stable dose of LMWH anticoagulant for at least 6 weeks 1week before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
- The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 7 days before the first dose of study treatment.
- The subject has uncontrolled, significant intercurrent or recent illness.
- Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment.
- Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment.
- Pregnant or lactating females.
- Inability to swallow tablets.
- Previously identified allergy or hypersensitivity to components of the study treatment formulations.
- Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Medstar Franklin Square Medical Center, Harry and Jeanette Weinberg Cancer Institute
Baltimore, Maryland, 21237
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007
About this study
Official title: Phase II Study of Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma
In this phase II advanced melanoma study, all patients will receive treatment with nivolumab/ipilimumab plus cabozantinib for a 12 week induction period followed by nivolumab plus cabozantinib maintanence to complete up to 2 years of therapy unless disease progression, dose limiting toxicity, provider/patient decision or patient withdrawal of consent occurs. The primary endpoint is the one year PFS rate. Patients will have staging scans at baseline and every 12 weeks during the first 2 years on study. Safety evaluations including labs, EKG and history and physical will occur at each visit. Baseline tumor sample is required and on treatment biopsy will be optional of superficial tumor in the skin, subcutaneous tissue or lymph node that is palpable.
Read the detailed description
Subjects will receive nivolumab, ipilimumab and cabozantinib until either disease progression, the occurrence of unacceptable drug-related toxicity or for other reason(s) for subject withdrawal. Treatment will continue for up to 2 years unless there is disease progression, drug intolerance or other reason for discontinuation discussed with the principal investigator (PI). Patients with ongoing complete or partial response may discontinue therapy after 1 year on treatment at the discretion of the treating investigator.
- Conditions
- Melanoma
- Being tested
- Nivolumab, Ipilimumab, Cabozantinib
- Keywords
- melanoma
- 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 Opdivo
Induction: 3mg/kg IV every 3 weeks x 4 cycles
Maintenance: 480mg IV every 4 weeks for up to 92 weeks
IpilimumabDrug
Also called Yervoy
Induction: 1mg/kg IV every 3 weeks x 4 cycles
CabozantinibDrug
Also called Cabometyx
Induction and Maintenance: 40mg PO daily
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Nivolumab 3mg/kg IV plus Ipilimumab 1mg/kg IV every 3 weeks x 4 cycles with Cabozantinib 40mg PO daily for 12 weeks (Induction); Followed by Maintenance therapy: Nivolumab 480mg IV every 4 weeks for up to 92 weeks; Cabozantinib 40mg PO daily for up to 92 weeks; Maintenance therapy will continue for up to 92 weeks to complete 2 years total of treatment if tolerating therapy well and disease is controlled. Receives: Drug: Nivolumab; Drug: Ipilimumab; Drug: Cabozantinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Progression Free Survival (PFS) for Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma.
The PFS rate for nivolumab/ipilimumab plus cabozantinib in patients with unresectable advanced melanoma using imRECIST.
Measured: 1 year
Secondary outcomes (3)
The Response Rate of Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma.
The ORR by imRECIST of nivolumab/ipilimumab plus cabozantinib in patients with unresectable advanced melanoma.
Measured: 1 year
The Overall Survival (OS) of Patients With Unresectable Advanced Melanoma Treated With Nivolumab/Ipilimumab Plus Cabozantinib.
The median and 3 year OS rate of patients with unresectable advanced melanoma treated with nivolumab/ipilimumab plus cabozantinib.
Measured: 3 years
The Incidence of Treatment-emergent Adverse Events of Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma.
The rate of all grade and grade 3-5 adverse events and the rate of discontinuation of study drug(s) due to adverse events.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2019
- Study start2 Mar 2020
- Primary completion8 Aug 2023
- Study completionDec 2026 (estimated)
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 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
- MedStar Franklin Square Medical Center, Hackensack Meridian Health, Exelixis
- Responsible party
- Sponsor
- Investigators
- Geoffrey T Gibney, MD, Principal investigator, MedStar Georgetown University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04091750
- Sponsor's protocol ID
- STUDY00000904
- Status last verified
- Feb 2026
- First submitted
- 13 Sep 2019
- Last updated
- 3 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma
- ClinicalTrials.gov ID
- NCT04091750
- Acronym / sponsor ID
- STUDY00000904
- Conditions
- Melanoma
- Keywords
- melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Georgetown UniversityUniversity, hospital or other
- Collaborators
- MedStar Franklin Square Medical Center, Hackensack Meridian Health, Exelixis
- Study start
- 2 Mar 2020 (actual)
- Primary completion
- 8 Aug 2023 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 17 Sep 2019 (actual)
- Results
- Posted 27 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this phase II advanced melanoma study, all patients will receive treatment with nivolumab/ipilimumab plus cabozantinib for a 12 week induction period followed by nivolumab plus cabozantinib maintanence to complete up to 2 years of therapy unless disease progression, dose limiting toxicity, provider/patient decision or patient withdrawal of consent occurs. The primary endpoint is the one year PFS rate. Patients will have staging scans at baseline and every 12 weeks during the first 2 years on study. Safety evaluations including labs, EKG and history and physical will occur at each visit. Baseline tumor sample is required and on treatment biopsy will be optional of superficial tumor in the skin, subcutaneous tissue or lymph node that is palpable.
Detailed description
Subjects will receive nivolumab, ipilimumab and cabozantinib until either disease progression, the occurrence of unacceptable drug-related toxicity or for other reason(s) for subject withdrawal. Treatment will continue for up to 2 years unless there is disease progression, drug intolerance or other reason for discontinuation discussed with the principal investigator (PI). Patients with ongoing complete or partial response may discontinue therapy after 1 year on treatment at the discretion of the treating investigator.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: Nivolumab, Drug: Ipilimumab, Drug: CabozantinibNivolumab 3mg/kg IV plus Ipilimumab 1mg/kg IV every 3 weeks x 4 cycles with Cabozantinib 40mg PO daily for 12 weeks (Induction); Followed by Maintenance therapy: Nivolumab 480mg IV every 4 weeks for up to 92 weeks; Cabozantinib 40mg PO daily for up to 92 weeks; Maintenance therapy will continue for up to 92 weeks to complete 2 years total of treatment if tolerating therapy well and disease is controlled. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- All patients must have unresectable stage IIIb-IIId or IV melanoma by AJCC 8th edition. Note: Patients with uveal melanoma are excluded from this study.
- Age > 18 and ECOG Performance Status of 0 or 1.
- Measurable disease by RECIST 1.1
- Baseline tumor specimen available.
- Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
Key exclusion criteria (19 listed)
- Prior treatment with anti-PD-1/PD-L1 therapy, anti-CTLA-4 therapy or cabozantinib. Prior adjuvant anti-PD-1 and/or anti-CTLA-4 therapy is allowed if relapse is greater than 6 months from last dose.
- Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
- Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
- Radiation therapy for bone metastasis or brain metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment.
- Known brain metastases that are >10mm or cranial epidural disease unless adequately treated with radiosurgery and/or surgery (including radiosurgery). Eligible subjects must be neurologically asymptomatic and without corticosteroid requirement. Dexamethasone < 2mg daily (or equivalent) will be allowed if discontinuation of corticosteroids is not feasible due to post-radiation effects and patient is asymptomatic. Patients with active, asymptomatic brain metastases that are <10mm and no corticosteroid requirement will be allowed without radiosurgery or surgery.
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: OpdivoInduction: 3mg/kg IV every 3 weeks x 4 cycles Maintenance: 480mg IV every 4 weeks for up to 92 weeks | Drug | Single Arm |
| IpilimumabAlso: YervoyInduction: 1mg/kg IV every 3 weeks x 4 cycles | Drug | Single Arm |
| CabozantinibAlso: CabometyxInduction and Maintenance: 40mg PO daily | Drug | Single Arm |
Primary outcome
The Progression Free Survival (PFS) for Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma.
Time frame: 1 year
The PFS rate for nivolumab/ipilimumab plus cabozantinib in patients with unresectable advanced melanoma using imRECIST.
3 secondary outcomes
The Response Rate of Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma.
Time frame: 1 year
The Overall Survival (OS) of Patients With Unresectable Advanced Melanoma Treated With Nivolumab/Ipilimumab Plus Cabozantinib.
Time frame: 3 years
The Incidence of Treatment-emergent Adverse Events of Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma.
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Geoffrey T Gibney, MD principal investigator
MedStar Georgetown University Hospital
3 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, Ipilimumab and Cabozantinib in people with Melanoma, run by Georgetown University at 3 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 9 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 3 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 27 Nov 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?
The Progression Free Survival (PFS) for Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma. (time frame: 1 year). 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 3 Mar 2026.