Clinical Trials /

BrUOG 324: Adjuvant Nivolumab and Low Dose Ipilimumab for Stage III and Resected Stage IV Melanoma: A Phase II Brown University Oncology Research Group Trial

NCT02656706

Description:

Effective adjuvant treatment can increase cure in patients with high-risk resected melanoma. High dose interferon is a standard of care in the adjuvant setting but is highly toxic and marginally effective. The combination of ipilimumab and nivolumab is the most active regimen in patients with advanced melanoma so there is clear rationale to test this regimen in the adjuvant setting. Investigators are testing if nivolumab 3mg/kg every 2 weeks with 1mg/kg ipilimumab every 6 weeks in the high risk adjuvant setting. The duration of therapy will be six months.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: BrUOG 324: Adjuvant Nivolumab and Low Dose Ipilimumab for Stage III and Resected Stage IV Melanoma: A Phase II Brown University Oncology Research Group Trial
  • Official Title:

Clinical Trial IDs

  • ORG STUDY ID: BrUOG 324
  • NCT ID: NCT02656706

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
IpilumumabAdjuvant treatment
NivolumabAdjuvant treatment

Purpose

Effective adjuvant treatment can increase cure in patients with high-risk resected melanoma. High dose interferon is a standard of care in the adjuvant setting but is highly toxic and marginally effective. The combination of ipilimumab and nivolumab is the most active regimen in patients with advanced melanoma so there is clear rationale to test this regimen in the adjuvant setting. Investigators are testing if nivolumab 3mg/kg every 2 weeks with 1mg/kg ipilimumab every 6 weeks in the high risk adjuvant setting. The duration of therapy will be six months.

Trial Arms

NameTypeDescriptionInterventions
Adjuvant treatmentExperimentalIpilumumab:1mg/kg q6weeks (1 dose per cycle, 4 planned treatments over 6 months total) Nivolumab:3mg/kg q2weeks (3 doses per cycle, 12 planned treatments over 6 months total)
  • Ipilumumab
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically proven melanoma. The primary site of melanoma may be
             cutaneous on other body site such as ocular or anorectal. Documentation required to be
             sent to BrUOG.

          -  Completely resected stage III (lymph node positive) or resected stage IV disease.
             Patients with stage T4BN0 are also eligible. It is required that patients with stage
             IIIA disease have > 1mm nodal involvement via pathology assessment of the resected
             node. All patients must be disease free to be eligible.

          -  No prior treatment for melanoma other than surgical resection or radiation. At least 4
             weeks since prior surgery and 3 weeks since prior radiation to registration date.

          -  Age >/= 18 years

          -  ECOG performance status 0-1

          -  Patients must have organ and marrow function as defined below within 14 days of study
             entry:

        Hematologic Absolute neutrophil count (ANC) >/= 1.5 X 109/L; Hemoglobin >/= 9.5 g/dL;
        Platelets >/= 100 X 109/L; Total Bilirubin ≤ 1.5 x ULN except subjects with normal direct
        bilirubin or those with known Gilbert's syndrome. Send information to BrUOG if patient has
        known Gilbert's syndrome AST and ALT </= 2.5 X ULN Albumin >/= 2.5 g/dL Renal Creatinine OR
        Calculated creatinine clearance : Creatinine </= 1.5 mg/dl or creatinine clearance >
        50ml/min

          -  No clinically significant coagulation disorder as defined by the treating MD.
             Therapeutic use of anticoagulants is permissible. Add to concomitant medication log if
             applicable.

          -  Not pregnant and not nursing. Women of child bearing potential must have a negative
             serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7
             days prior to Day 1 of treatment. Post-menopausal women (surgical menopause or lack of
             menses >12 months) do not need to have a pregnancy test, please document status.

          -  Confirmation of informed consent.

          -  Men and women of childbearing potential enrolled in this study must agree to use
             adequate barrier birth control measures during the course of the study and up to 2
             months after end of treatment.

        Exclusion Criteria:

          -  Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or
             biologic therapy) or investigational anti-cancer drug

          -  Brain metastases, whether resected or not, and any known leptomeningeal disease or
             known bone metastases.

          -  Pregnant or breastfeeding female

          -  Unwillingness or inability to follow the procedures required in the protocol, to
             document

          -  Any serious or uncontrolled medical disorder that, in the opinion of the investigator,
             may increase the risk associated with study participation or study drug
             administration, impair the ability of the subject to receive protocol therapy, or
             interfere with the interpretation of study results.

          -  Prior malignancy active within the previous 2 years except for locally curable cancers
             that have been apparently cured, such as basal or squamous cell skin cancer,
             superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
             Documentation required to be sent to BrUOG

          -  Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,
             controlled type I diabetes mellitus, residual hypothyroidism due to autoimmune
             condition only requiring hormone replacement, psoriasis not requiring systemic
             treatment, or conditions not expected to recur in the absence of an external trigger
             are permitted to enroll.

          -  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 >10mg daily of prednisone equivalents are permitted in the absence of active
             autoimmune disease.

          -  Prior treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody

          -  Any positive test result for hepatitis B or C virus indicating acute or chronic
             infection

          -  Known history of testing positive for human immunodeficiency virus or known acquired
             immunodeficiency syndrome

          -  History of severe hypersensitivity reaction to any monoclonal antibody.

          -  Patients with unstable angina (anginal symptoms at rest) or new-onset angina (began
             within the last 3 months) or myocardial infarction within the past 6 months.

          -  History of autologous transplant or organ allograft even if not taking
             immunosuppressive medications
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Toxicity of nivolumab and low-dose ipilimumab as adjuvant therapy for patients with high risk melanoma.
Time Frame:From day 1 of treatment through 30 days post the last dose of drug, for a total of about 7 months.
Safety Issue:
Description:A rate of 35% or greater grade 3 or grade 4 treatment related non-hematologic toxicities or grade 4 neutropenia or thrombocytopenia, or grade 2 treatment related toxicities that prevent the completion of treatment will be considered to be unacceptable.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Maria Constantinou

Trial Keywords

  • Adjuvant melanoma
  • Advanced melanoma

Last Updated