Clinical Trials /

Ipilimumab and Nivolumab as Adjuvant Treatment of Mucosal Melanoma

NCT03241186

Description:

This is a single arm phase II clinical trial of Ipilimumab and Nivolumab in patients with resected mucosal melanoma. Ipilimumab (1 mg/kg) and Nivolumab (3 mg/kg) will be administered Day 1 of a 21-day cycle in Cycles 1-4 and then nivolumab 480 mg will be administered Day 1 of a 28-day cycle for Cycles 5-15 (maximum of 15) or until disease recurrence or intolerance before completion of 15 cycles.

Related Conditions:
  • Mucosal Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ipilimumab and Nivolumab as Adjuvant Treatment of Mucosal Melanoma
  • Official Title: Single Arm Phase II Study of Ipilimumab and Nivolumab as Adjuvant Therapy for Resected Mucosal Melanoma (SALVO Study). HCRN: MEL16-252

Clinical Trial IDs

  • ORG STUDY ID: MEL16-252
  • NCT ID: NCT03241186

Conditions

  • Mucosal Melanoma

Interventions

DrugSynonymsArms
IpilimumabYervoy, BMS-734016, MDX010Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IV
NivolumabOPDIVO, BMS-936558, ONO-4538, MDX1106Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IV
NivolumabOPDIVO, BMS-936558, ONO-4538, MDX1106Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IV

Purpose

The trial is a single arm phase II clinical trial of Ipilimumab and Nivolumab in patients with resected mucosal melanoma. Ipilimumab (1 mg/kg) and Nivolumab (3 mg/kg) will be administered day 1 of a 21-day cycle in cycles 1-4 and then nivolumab 480 mg will be administered day 1 of a 28-day cycle for cycles 5-15 or until disease recurrence.

Detailed Description

      Ipilimumab and Nivolumab Combination Administration

        -  Ipilimumab 1mg/kg given IV Day 1 for 3 weeks (21 days), for 4 cycles

        -  Nivolumab 3mg/kg given IV Day 1 for 3 weeks (21 days), for 4 cycles

      Nivolumab Alone Administration

        -  Nivolumab 480mg given IV Day 1 for 4 weeks (28 days), for 5-15 cycles

      Nivolumab is to be administered as an approximately 30-minute IV infusion (± 10 minutes). At
      the end of the infusion, flush the line with a sufficient quantity of normal saline.

      Ipilimumab is to be administered as an approximately 30-minute IV infusion (± 10 minutes). At
      the end of the infusion, flush the line with a sufficient quantity of normal saline or 5%
      dextrose solution.

      When both study drugs are to be administered on the same day, separate infusion bags and
      filters must be used for each infusion. Nivolumab is to be administered first. The nivolumab
      infusion must be promptly followed by a saline flush to clear the line of nivolumab before
      starting the ipilimumab infusion. The second infusion will always be ipilimumab, and will
      start at least 30 minutes after completion of the nivolumab infusion.

      The dosing calculations should be based on the body weight from Cycle 1 Day 1. If the
      subject's weight on the day of dosing differs by > 5% from the weight used to calculate the
      dose, the dose should be recalculated based on the current day of treatment weight. All doses
      should be rounded to the nearest milligram. There will be no dose modifications allowed.
    

Trial Arms

NameTypeDescriptionInterventions
Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IVExperimentalCycles 1-4: Ipilimumab (1 mg/kg) + Nivolumab (3 mg/kg) IV Day 1 of each Cycle Each Cycle = 21 days Cycles 5-15: Nivolumab IV 480 mg Day 1 of each Cycle Each Cycle = 28 days
  • Ipilimumab
  • Nivolumab
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

        Subject must meet all of the following applicable inclusion criteria to participate in this
        study:

          -  Histological confirmation of melanoma of any mucosal site including (but not limited
             to) anus/rectum, vulvar/vaginal, sinonasal. NOTE: Melanomas of cutaneous origin and/or
             ocular origin are ineligible.

          -  R0 or R1 resection of primary melanoma tumor (no gross disease can be left behind, but
             microscopically positive margins are acceptable).

          -  Surgery within ≤ 90 days of registration.

          -  ECOG Performance Status (PS) ≤ 1

        The following laboratory values obtained ≤ 14 days prior to registration:

        Hematological:

          -  Absolute Neutrophil Count (ANC) ≥ 1500/mm^3

          -  Hemoglobin (Hgb) ≥ 9 g/dL (may be transfused)

          -  Platelet (Plt) 100,000/mm^3

        Renal:

          -  Serum Creatinine ≤ 1.5 x ULN

        Hepatic:

          -  Alkaline Phosphatase (Alk Phos) ≤ 1.5 x upper limit of normal (ULN)

          -  Total and Direct Bilirubin ≤ 1.5 × (ULN)

          -  Aspartate aminotransferase (AST) ≤ 1.5 × ULN

          -  Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing
             potential only. NOTE: Females are considered of child bearing potential unless they
             are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or
             bilateral oophorectomy) or they are naturally postmenopausal for at least 12
             consecutive months.

          -  Written informed consent and HIPAA authorization for release of personal health
             information prior to registration. NOTE: HIPAA authorization may be included in the
             informed consent or obtained separately.

          -  Willing to return to enrolling institution for follow-up

          -  Willing to provide tissue and/or blood samples for correlative research purposes

        Exclusion Criteria:

        Subjects meeting any of the criteria below may not participate in the study:

          -  Any of the following because this study involves: an agent that has likely genotoxic,
             mutagenic, and teratogenic effects:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to use adequate
                  contraception

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the subject inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens.

          -  Immunocompromised patients and subjects known to be HIV positive and currently
             receiving antiretroviral therapy. NOTE: Subjects known to be HIV positive, but without
             clinical evidence of an immunocompromised state, are eligible for this trial.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm.

          -  Other active malignancy ≤ 3 years prior to registration. EXCEPTIONS: Malignancies with
             a very low (< 5%) risk of recurrence such as non-melanotic skin cancer or
             carcinoma-in-situ of the cervix.

          -  History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use
             of ongoing maintenance therapy for life-threatening ventricular arrhythmias.

          -  Active autoimmune disease -including but not limited to:

               -  Subjects with a history of inflammatory bowel disease, including ulcerative
                  colitis and Crohn's Disease,

               -  Subjects with a history of symptomatic autoimmune disease requiring systemic
                  treatment within the past 2 years with the use of disease modifying agents,
                  corticosteroids, or immunosuppressive drugs.

                    -  rheumatoid arthritis,

                    -  systemic progressive sclerosis (scleroderma),

                    -  systemic lupus erythematosus,

                    -  psoriasis,

                    -  autoimmune vasculitis (e.g., Wegener's Granulomatosis),

                    -  CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-
                       Barre Syndrome and Myasthenia Gravis, multiple sclerosis).

        EXCEPTION: autoimmune conditions that are only requiring replacement therapy (e.g.,
        thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or
        pituitary insufficiency, etc.) is not considered a form of systemic treatment.

          -  Any radiation within 2 weeks prior to study initiation. Neoadjuvant and adjuvant
             radiation are allowed, but must be completed > 2 weeks prior to registration.

          -  Any prior systemic therapy for melanoma (chemotherapy, immunotherapy, targeted
             therapy)

          -  Women of childbearing potential (WOCBP) and males must be willing to abstain from
             heterosexual activity or to use 2 forms of effective methods of contraception from the
             time of informed consent until 5 months after the last dose of study drug. The two
             contraception methods can be comprised of two barrier methods, or a barrier method
             plus a hormonal method. Examples include: intrauterine device (IUD), vasectomy of a
             female subject's male partner, contraceptive rod implanted into the skin, or use of
             two of the following: diaphragm with spermicide (cannot be used in conjunction with
             cervical cap/spermicide), cervical cap with spermicide (nulliparous women only),
             contraceptive sponge (nulliparous women only), male condom or female condom (cannot be
             used together), hormonal contraceptive.*Abstinence is acceptable if this is the usual
             lifestyle and preferred contraception for the subject.

          -  Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
             mother is being treated on study).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Assess Recurrence-free survival time (RFS)
Time Frame:1.5 years
Safety Issue:
Description:Time from registration to documentation of first disease recurrence or death due to any cause.

Secondary Outcome Measures

Measure:Assess the Adverse Events
Time Frame:2 years
Safety Issue:
Description:Adverse events will be graded and attribution assigned using CTCAE version 4
Measure:Overall Survival (OS)
Time Frame:2 years
Safety Issue:
Description:The time from registration to death due to any cause

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Robert R. McWilliams, MD

Trial Keywords

  • Ipilimumab
  • Nivolumab
  • OPDIVO
  • IgG4 kappa immunoglobulin

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