Study of Combination of Ipilimumab and Nivolumab in Patients With Melanoma

Sponsor
NYU Langone Health (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02970981
Collaborator
Bristol-Myers Squibb (Industry)
16
Enrollment
1
Location
1
Arm
62.1
Anticipated Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and tolerability of treatment with Nivolumab in combination with Ipilimumab in subjects with resected Stages IIIB/IIIC/ IV melanoma.

Condition or DiseaseIntervention/TreatmentPhase
  • Biological: Nivolumab
  • Biological: Ipilimumab
Phase 2

Detailed Description

The investigators hypothesize that PD-1 blockade combined with CTLA-4 blockade using ipilimumab would have a favorable effect on the expansion and activity of human CD8+ T cytotoxic lymphocytes (CTLs) specific for tumor-associated antigens (ie, self antigens), which would translate into improved anti-cancer therapy.

Study Design

Study Type:
Interventional
Actual Enrollment :
16 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Pilot Trial of Ipilimumab With Nivolumab for Participants With Resected Stages IIIB/IIIC/ IV Melanoma
Actual Study Start Date :
Nov 29, 2016
Actual Primary Completion Date :
Nov 1, 2018
Anticipated Study Completion Date :
Feb 1, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Nivolumab and Ipilimumab

Dosing during cycle 1 will consist of: 3 mg/kg of Nivolumab+ Ipilimumab at 1 mg/kg. Each induction treatment cycle is comprised of 4 doses of Nivolumab and 4 doses of Ipilimumab given every three weeks for a total of 12 weeks (cycle 1) Dosing during cycles 2-5 will consist of flat dose Nivolumab at 480 mg every 4 weeks (Q4W) for 48 weeks.

Biological: Nivolumab
Other Names:
  • Opdivo
  • NSC 748726
  • Biological: Ipilimumab
    Other Names:
  • Yervoy
  • NSC 732442
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Cases of Adverse Events Occurring During Study [12 weeks post-treatment start]

      The adverse events are evaluated per Common Terminology Criteria for Adverse Events (CTCAE) V4.

    Secondary Outcome Measures

    1. Time to Relapse [Up to 4 years]

      Time to relapse will be reported (in months post-treatment) to assess the preliminary efficacy of the study drugs.

    2. Immune Response Assessment [12 Weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    16 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Be at least 16 years of age;

    • Histologic diagnosis of resected Stages IIIB/IIIC/ IV melanoma, with no evidence of disease clinically and radiologically, and negative surgical margins. All melanomas regardless of primary site of disease will be allowed;

    • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

    • Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) must have been completed at least 4 weeks before study drug administration, and all adverse events have either returned to baseline or stabilized;

    • Prior treated brain or meningeal metastases must be without magnetic resonance imaging (MRI) evidence of progression for at least 8 weeks and off immunosuppressive doses of systemic steroids (> 10 mg/day prednisone or equivalent) for at least 2 weeks before study drug administration;

    • Prior systemic radiation therapy must have been completed at least 4 weeks before study drug administration. Prior focal radiotherapy completed at least 2 weeks before study drug administration. No radiopharmaceuticals (strontium, samarium) within 8 weeks before study drug administration;

    • Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration;

    • Completed nitrosourea treatment at least 6 weeks before administration of any study drug;

    • Prior surgery that required general anesthesia must be completed at least 4 weeks before study drug administration. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration and subjects should be recovered;

    • Screening laboratory values must meet the following criteria:

    white blood cells (WBCs) ≥ 2000 cells/μL

    • neutrophils ≥ 1500 cells/μL

    • platelets ≥ 100 x 103/μL

    • hemoglobin ≥ 9.0 g/dL

    • serum creatinine ≤ 2 mg/dL

    • AST ≤ 2.5 x upper limit of normal (ULN) without, and ≤ 5 x ULN with hepatic metastasis

    • ALT ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis

    • bilirubin ≤ 2 x ULN (except subjects with Gilbert's syndrome, who must have total bilirubin < 3.0 mg/dL)

    • Females of childbearing potential must:

    • use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.

    • Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab.

    • For female subjects to be considered as not having childbearing potential, they must meet 1 or more of the following criteria:

    • postmenopausal for at least 24 consecutive months;

    • surgically sterile (ie, have had a hysterectomy or bilateral oophorectomy);

    • females with irregular menstrual periods and/or on hormone replacement therapy must have a documented serum follicle stimulating hormone level > 35 mIU/mL;

    • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception.

    • Subject must have read, understood, and provided written informed consent and HIPAA authorization after the nature of the study has been fully explained; and

    • Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

    Exclusion Criteria:
    • Subjects who fulfill any of the following conditions at Screening will not be eligible for admission into the study:

    • History of severe hypersensitivity reactions to other mAbs;

    • Prior non-melanoma 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;

    • Subjects with any active autoimmune disease (Appendix 3) or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy;

    • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);

    • Positive tests for hepatitis B virus surface antigen (HBV SAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection;

    • Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or any other antibody targeting T cell co-stimulation pathways);

    • Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids;

    • Underlying medical condition (eg, a condition associated with diarrhea) that, in the Investigator's opinion, would make the administration of either study drug or both study drugs hazardous to the subject or obscure the interpretation of toxicity determination or adverse events;

    • Pregnant or nursing; or

    • Current participation in another clinical study involving treatment with medications, radiation or surgery, or prior participation in this study.

    • Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.

    As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.

    • Allergies and Adverse Drug Reaction
    1. History of allergy to study drug components

    2. History of severe hypersensitivity reaction to any monoclonal antibody

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Laura and Isaac Perlmutter Cancer CenterNew YorkNew YorkUnited States10016

    Sponsors and Collaborators

    • NYU Langone Health
    • Bristol-Myers Squibb

    Investigators

    • Principal Investigator: Jeffrey S Weber, MD, PhD, NYU Perlmutter Cancer Center

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    NYU Langone Health
    ClinicalTrials.gov Identifier:
    NCT02970981
    Other Study ID Numbers:
    • 16-00098
    First Posted:
    Nov 22, 2016
    Last Update Posted:
    Jan 25, 2022
    Last Verified:
    Jan 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by NYU Langone Health
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleNivolumab and Ipilimumab
    Arm/Group DescriptionDosing during cycle 1 will consist of: 3 mg/kg of Nivolumab+ Ipilimumab at 1 mg/kg. Each induction treatment cycle is comprised of 4 doses of Nivolumab and 4 doses of Ipilimumab given every three weeks for a total of 12 weeks (cycle 1) Dosing during cycles 2-5 will consist of flat dose Nivolumab at 480 mg every 4 weeks (Q4W) for 48 weeks. Nivolumab Ipilimumab
    Period Title: Overall Study
    STARTED16
    COMPLETED16
    NOT COMPLETED0

    Baseline Characteristics

    Arm/Group TitleNivolumab and Ipilimumab
    Arm/Group DescriptionDosing during cycle 1 will consist of: 3 mg/kg of Nivolumab+ Ipilimumab at 1 mg/kg. Each induction treatment cycle is comprised of 4 doses of Nivolumab and 4 doses of Ipilimumab given every three weeks for a total of 12 weeks (cycle 1) Dosing during cycles 2-5 will consist of flat dose Nivolumab at 480 mg every 4 weeks (Q4W) for 48 weeks. Nivolumab Ipilimumab
    Overall Participants16
    Age, Customized (Count of Participants)
    >= 16 years
    16
    100%
    Sex: Female, Male (Count of Participants)
    Female
    2
    12.5%
    Male
    14
    87.5%
    Race and Ethnicity Not Collected (Count of Participants)
    Disease Stage at Entry (Count of Participants)
    IIIB
    6
    37.5%
    IIIC
    5
    31.3%
    IV
    4
    25%
    IIB
    1
    6.3%

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Cases of Adverse Events Occurring During Study
    DescriptionThe adverse events are evaluated per Common Terminology Criteria for Adverse Events (CTCAE) V4.
    Time Frame12 weeks post-treatment start

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleNivolumab and Ipilimumab
    Arm/Group DescriptionDosing during cycle 1 will consist of: 3 mg/kg of Nivolumab+ Ipilimumab at 1 mg/kg. Each induction treatment cycle is comprised of 4 doses of Nivolumab and 4 doses of Ipilimumab given every three weeks for a total of 12 weeks (cycle 1) Dosing during cycles 2-5 will consist of flat dose Nivolumab at 480 mg every 4 weeks (Q4W) for 48 weeks. Nivolumab Ipilimumab
    Measure Participants16
    Number [cases of adverse events]
    238
    2. Secondary Outcome
    TitleTime to Relapse
    DescriptionTime to relapse will be reported (in months post-treatment) to assess the preliminary efficacy of the study drugs.
    Time FrameUp to 4 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    3. Secondary Outcome
    TitleImmune Response Assessment
    Description
    Time Frame12 Weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame12 weeks post-treatment
    Adverse Event Reporting Description
    Arm/Group TitleNivolumab and Ipilimumab
    Arm/Group DescriptionDosing during cycle 1 will consist of: 3 mg/kg of Nivolumab+ Ipilimumab at 1 mg/kg. Each induction treatment cycle is comprised of 4 doses of Nivolumab and 4 doses of Ipilimumab given every three weeks for a total of 12 weeks (cycle 1) Dosing during cycles 2-5 will consist of flat dose Nivolumab at 480 mg every 4 weeks (Q4W) for 48 weeks. Nivolumab Ipilimumab
    All Cause Mortality
    Nivolumab and Ipilimumab
    Affected / at Risk (%)# Events
    Total0/16 (0%)
    Serious Adverse Events
    Nivolumab and Ipilimumab
    Affected / at Risk (%)# Events
    Total4/16 (25%)
    Blood and lymphatic system disorders
    Hyponatremia1/16 (6.3%) 1
    Gastrointestinal disorders
    Enterocolitis1/16 (6.3%) 1
    Diarrhea1/16 (6.3%) 1
    General disorders
    Fever1/16 (6.3%) 1
    Fatigue1/16 (6.3%) 1
    Musculoskeletal and connective tissue disorders
    Generalized Muscle Weakness1/16 (6.3%) 1
    Other (Not Including Serious) Adverse Events
    Nivolumab and Ipilimumab
    Affected / at Risk (%)# Events
    Total16/16 (100%)
    Blood and lymphatic system disorders
    Anemia4/16 (25%)
    Edema2/16 (12.5%)
    Decrease in platelet count1/16 (6.3%)
    Eye disorders
    Conjunctivitis1/16 (6.3%)
    Green floater in eye1/16 (6.3%)
    Gastrointestinal disorders
    Abdominal Pain3/16 (18.8%)
    Bloating2/16 (12.5%)
    Constipation2/16 (12.5%)
    Diarrhea6/16 (37.5%)
    Enterocolitis2/16 (12.5%)
    GERD2/16 (12.5%)
    Loose stool7/16 (43.8%)
    Mucositis oral1/16 (6.3%)
    Vomiting4/16 (25%)
    General disorders
    Increase in Alkalina Phosphatase1/16 (6.3%)
    Allergic rhinitis2/16 (12.5%)
    Blurred vision2/16 (12.5%)
    Chills3/16 (18.8%)
    Dehydration1/16 (6.3%)
    Dry mouth2/16 (12.5%)
    Fever2/16 (12.5%)
    Alopecia1/16 (6.3%)
    Malaise1/16 (6.3%)
    Nasal congestion5/16 (31.3%)
    Non productive cough1/16 (6.3%)
    Nausea6/16 (37.5%)
    General pain9/16 (56.3%)
    Productive cough2/16 (12.5%)
    Hepatobiliary disorders
    Increase in alanine aminotransferase3/16 (18.8%)
    Infections and infestations
    Sore throat3/16 (18.8%)
    Metabolism and nutrition disorders
    Increase in Creatinine1/16 (6.3%)
    Musculoskeletal and connective tissue disorders
    Cramping2/16 (12.5%)
    Hernia1/16 (6.3%)
    Myalgia5/16 (31.3%)
    Psychiatric disorders
    Anorexia1/16 (6.3%)
    Renal and urinary disorders
    Urinary urgency1/16 (6.3%)
    Respiratory, thoracic and mediastinal disorders
    Chest wall discomfort1/16 (6.3%)
    Skin and subcutaneous tissue disorders
    Papulopostular rash3/16 (18.8%)
    Pruritis16/16 (100%) 17
    Rash maculopapular16/16 (100%) 30

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleJeffrey S. Weber, MD, PhD
    OrganizationNYU Langone Health - Perlmutter Cancer Center
    Phone212 731 6262
    EmailJeffrey.Weber@nyulangone.org
    Responsible Party:
    NYU Langone Health
    ClinicalTrials.gov Identifier:
    NCT02970981
    Other Study ID Numbers:
    • 16-00098
    First Posted:
    Nov 22, 2016
    Last Update Posted:
    Jan 25, 2022
    Last Verified:
    Jan 1, 2022