Study of Combination of Ipilimumab and Nivolumab in Patients With Melanoma

NCT02970981 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-00098
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma

Keywords

Monoclonal antibody; Programmed Death-1 (PD-1); Programmed Death-Ligand 1 (PD-L1); Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4); Antigen

Outcome Measures

Primary Outcomes (1)

• Relapse-Free Survival

  Number of participants who are relapse-free at 48 months after initiating treatment in the study.

  Month 48 Post-Treatment Initiation

Secondary Outcomes (2)

• Number of Cases of Adverse Events Occurring During Study

  Month 12 Post-Treatment Initiation

• Overall Survival

  Month 48 Post-Treatment Initiation

Study Arms (1)

Nivolumab and Ipilimumab

EXPERIMENTAL

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; Biological: Ipilimumab

Interventions

Nivolumab BIOLOGICAL

Also known as: Opdivo, NSC 748726

Nivolumab and Ipilimumab

Ipilimumab BIOLOGICAL

Also known as: Yervoy, NSC 732442

Nivolumab and Ipilimumab

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• NYU Langone Health: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Laura and Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Related Publications (1)

• Khushalani NI, Vassallo M, Goldberg JD, Eroglu Z, Kim Y, Cao B, Ferguson R, Monson KR, Kirchhoff T, Amato CM, Burke P, Strange A, Monk E, Gibney GT, Kudchadkar R, Markowitz J, Brohl AS, Pavlick A, Richards A, Woods DM, Weber J. Phase II clinical and immune correlate study of adjuvant nivolumab plus ipilimumab for high-risk resected melanoma. J Immunother Cancer. 2022 Nov;10(11):e005684. doi: 10.1136/jitc-2022-005684.

  PMID: 36450385 DERIVED

MeSH Terms

Conditions

Melanoma; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jeffrey S. Weber, MD, PhD
• Organization: NYU Langone Health - Perlmutter Cancer Center

Jeffrey.Weber@nyulangone.org

212 731 6262

Study Officials

• Jeffrey S Weber, MD, PhD

  NYU Perlmutter Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2016
• First Posted: November 22, 2016
• Study Start: November 29, 2016
• Primary Completion: November 1, 2018
• Study Completion: May 2, 2022
• Last Updated: April 30, 2024
• Results First Posted: March 11, 2020

Record last verified: 2024-04

Locations

US (1)