Clinical Trials /

Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma

NCT04091750

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma
  • Official Title: Phase II Study of Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma

Clinical Trial IDs

  • ORG STUDY ID: IST83
  • NCT ID: NCT04091750

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
NivolumabOpdivoSingle Arm
IpilimumabYervoySingle Arm
CabozantinibCabometyxSingle Arm

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Single ArmExperimentalInduction phase: Nivolumab 3mg/kg IV plus Ipilimumab 1mg/kg IV every 3 weeks x 4 cycles (12 week period) Cabozantinib 40mg PO daily for 12 weeks Maintenance phase: 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.
  • Nivolumab
  • Ipilimumab
  • Cabozantinib

Eligibility Criteria

        Inclusion Criteria:

          1. All patients must have unresectable stage IIIb-IIId or IV melanoma by AJCC 8th
             edition.

          2. Age > 18 and ECOG Performance Status of 0 or 1.

          3. Measurable disease by RECIST 1.1 and a tumor site amenable for on treatment biopsy.

          4. Baseline tumor specimen available.

          5. 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.

          6. Adequate organ and marrow function.

          7. Capable of understanding and complying with the protocol requirements and must have
             signed the informed consent document.

          8. 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.

          9. Female subjects of childbearing potential must not be pregnant at screening.

        Exclusion Criteria:

          1. 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.

          2. Receipt of any type of small molecule kinase inhibitor (including investigational
             kinase inhibitor) within 2 weeks before first dose of study treatment.

          3. Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy
             (including investigational) within 4 weeks before first dose of study treatment.

          4. 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.

          5. 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.

          6. History of active autoimmune disorder requiring immunosuppressive agents. Patients
             with autoimmune disorders considered low risk, such as vitiligo and thyroiditis, will
             be allowed.

          7. Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin
             and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel).

             Allowed anticoagulants are the following:

               1. Low-dose aspirin for cardioprotection (per local applicable guidelines) is
                  permitted.

               2. Low-dose low molecular weight heparins (LMWH) are permitted.

               3. Anticoagulation with therapeutic doses of LMWH is allowed in subjects without
                  known brain metastases who are on a stable dose of LMWH for at least 6 weeks
                  before first dose of study treatment, and who have had no clinically significant
                  hemorrhagic complications from the anticoagulation regimen or the tumor.

          8. 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.

          9. The subject has uncontrolled, significant intercurrent or recent illness.

         10. Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks
             before first dose of study treatment.

         11. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per
             electrocardiogram (ECG) within 28 days before first dose of study treatment.

         12. Pregnant or lactating females.

         13. Inability to swallow tablets.

         14. Previously identified allergy or hypersensitivity to components of the study treatment
             formulations.

         15. 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.

         16. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The progression free survival (PFS) for nivolumab/ipilimumab plus cabozantinib in patients with unresectable advanced melanoma.
Time Frame:1 year
Safety Issue:
Description:The PFS rate for nivolumab/ipilimumab plus cabozantinib in patients with unresectable advanced melanoma using imRECIST.

Secondary Outcome Measures

Measure:The response rate of nivolumab/ipilimumab plus cabozantinib in patients with unresectable advanced melanoma.
Time Frame:1 year
Safety Issue:
Description:The ORR by imRECIST of nivolumab/ipilimumab plus cabozantinib in patients with unresectable advanced melanoma.
Measure:The overall survival (OS) of patients with unresectable advanced melanoma treated with nivolumab/ipilimumab plus cabozantinib.
Time Frame:3 years
Safety Issue:
Description:The median and 3 year OS rate of patients with unresectable advanced melanoma treated with nivolumab/ipilimumab plus cabozantinib.
Measure:The incidence of treatment-emergent adverse events of nivolumab/ipilimumab plus cabozantinib in patients with unresectable advanced melanoma.
Time Frame:2 years
Safety Issue:
Description:The rate of all grade and grade 3-5 adverse events and the rate of discontinuation of study drug(s) due to adverse events.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Georgetown University

Trial Keywords

  • melanoma

Last Updated

November 4, 2020