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Study of Combination of Ipilimumab and Nivolumab in Patients With Melanoma

Primary Purpose

Melanoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nivolumab
Ipilimumab
Sponsored by
NYU Langone Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Monoclonal antibody, Programmed Death-1 (PD-1), Programmed Death-Ligand 1 (PD-L1), Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), Antigen

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Laura and Isaac Perlmutter Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nivolumab and Ipilimumab

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of Cases of Adverse Events Occurring During Study
The adverse events are evaluated per Common Terminology Criteria for Adverse Events (CTCAE) V4.

Secondary Outcome Measures

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

Full Information

First Posted
November 18, 2016
Last Updated
August 11, 2022
Sponsor
NYU Langone Health
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT02970981
Brief Title
Study of Combination of Ipilimumab and Nivolumab in Patients With Melanoma
Official Title
A Pilot Trial of Ipilimumab With Nivolumab for Participants With Resected Stages IIIB/IIIC/ IV Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
November 29, 2016 (Actual)
Primary Completion Date
November 2018 (Actual)
Study Completion Date
May 2, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
Collaborators
Bristol-Myers Squibb

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Monoclonal antibody, Programmed Death-1 (PD-1), Programmed Death-Ligand 1 (PD-L1), Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), Antigen

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nivolumab and Ipilimumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo, NSC 748726
Intervention Type
Biological
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
Yervoy, NSC 732442
Primary Outcome Measure Information:
Title
Number of Cases of Adverse Events Occurring During Study
Description
The adverse events are evaluated per Common Terminology Criteria for Adverse Events (CTCAE) V4.
Time Frame
12 weeks post-treatment start
Secondary Outcome Measure Information:
Title
Time to Relapse
Description
Time to relapse will be reported (in months post-treatment) to assess the preliminary efficacy of the study drugs.
Time Frame
Up to 4 years
Title
Immune Response Assessment
Time Frame
12 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 History of allergy to study drug components History of severe hypersensitivity reaction to any monoclonal antibody
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey S Weber, MD, PhD
Organizational Affiliation
NYU Perlmutter Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Laura and Isaac Perlmutter Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Study of Combination of Ipilimumab and Nivolumab in Patients With Melanoma

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