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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02656706
Recruitment Status : Unknown
Verified December 2018 by Maria Constantinou, Brown University.
Recruitment status was:  Recruiting
First Posted : January 15, 2016
Last Update Posted : December 19, 2018
Brown University
Rhode Island Hospital
The Miriam Hospital
Information provided by (Responsible Party):
Maria Constantinou, Brown University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Melanoma Drug: Ipilumumab Drug: Nivolumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : July 2016
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma
Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Adjuvant treatment
Ipilumumab: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)
Drug: Ipilumumab
Drug: Nivolumab

Primary Outcome Measures :
  1. 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. ]
    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.

  2. Recurrence-free and survival overall following adjuvant nivolumab and low dose ipilimumab for patients with high risk melanoma. [ Time Frame: Post treatment for up to 5 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02656706

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Contact: kayla Rosati, EdM 4018633000

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United States, Rhode Island
Rhode Island Hospital and The Miriam Hospital Recruiting
Providence, Rhode Island, United States, 02903/02906
Contact: Kayla Rosati, RI    401-863-3000   
Principal Investigator: Howard Safran, MD         
Sub-Investigator: Maria Constantinou, MD         
Sponsors and Collaborators
Maria Constantinou
Brown University
Rhode Island Hospital
The Miriam Hospital
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Responsible Party: Maria Constantinou, Principal Investigator, Brown University Identifier: NCT02656706    
Other Study ID Numbers: BrUOG 324
First Posted: January 15, 2016    Key Record Dates
Last Update Posted: December 19, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Maria Constantinou, Brown University:
Adjuvant melanoma
Advanced melanoma
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents, Immunological
Antineoplastic Agents