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A Study of Two Different Dose Combinations of Nivolumab in Combination With Ipilimumab in Subjects With Previously Untreated, Unresectable or Metastatic Melanoma

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.
 
ClinicalTrials.gov Identifier: NCT02714218
Recruitment Status : Active, not recruiting
First Posted : March 21, 2016
Results First Posted : April 23, 2019
Last Update Posted : October 1, 2019
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Brief Summary:
The purpose of this study is to evaluate two different dose combinations of nivolumab and ipilimumab in the treatment of melanoma.

Condition or disease Intervention/treatment Phase
Melanoma Biological: Nivolumab 3 mg/kg IV Biological: Ipilimumab 1 mg/kg IV Biological: Nivolumab 1 mg/kg IV Biological: Ipilimumab 3 mg/kg IV Biological: Nivolumab 6 mg/kg IV Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 481 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase IIIb/IV, Randomized, Double Blinded, Study of Nivolumab 3 mg/kg in Combination With Ipilimumab 1 mg/kg vs Nivolumab 1 mg/kg in Combination With Ipilimumab 3 mg/kg in Subjects With Previously Untreated, Unresectable or Metastatic Melanoma
Actual Study Start Date : March 24, 2016
Actual Primary Completion Date : April 20, 2017
Estimated Study Completion Date : April 15, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Nivolumab 3 mg/kg IV + Ipilimumab 1 mg/kg IV
Specified dose on specified days
Biological: Nivolumab 3 mg/kg IV
Followed by Nivolumab monotherapy

Biological: Ipilimumab 1 mg/kg IV
Followed by Nivolumab monotherapy

Experimental: Ipilimumab 3 mg/kg IV + Nivolumab 1 mg/kg IV
Specified dose on specified days
Biological: Nivolumab 1 mg/kg IV
Biological: Ipilimumab 3 mg/kg IV
Experimental: Nivolumab 6 mg/kg IV + Ipilimumab 1 mg/kg
Specified dose on specified days
Biological: Ipilimumab 1 mg/kg IV
Followed by Nivolumab monotherapy

Biological: Nivolumab 6 mg/kg IV
A dose of 240mg is identical to a dose of 3mg/kg, therefore 6mg/kg is approximately equal to ~ 480mg.




Primary Outcome Measures :
  1. Percentage of Participants With Drug-related Grade 3 - 5 Adverse Events (AEs) [ Time Frame: After first dose of study treatment and within 30 days of the last dose of study treatment ]
    The drug-related Grade 3 - 5 AE rate was defined as number of participants who experienced at least 1 AE of Grade 3 or higher, judged to be related to study drug by the investigator, and with onset on or after the first dose of study treatment and within 30 days of the last dose of study treatment, divided by number of treated participants. AE grade was defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: From date of randomization to date of objectively documented progression per RECIST 1.1 or the date of subsequent anti-cancer therapy, whichever occurs first (assessed up to April 2018, approximately 20 months) ]
    The ORR was defined as the number of participants with a best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of treated participants for each arm. The BOR was defined as the best response designation, as determined by the Investigator, recorded between the date of randomization and the date of progression, as assessed by the Investigator per RECIST 1.1 or the date of subsequent anticancer therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurred first. For participants without evidence of RECIST 1.1 progression or subsequent anticancer therapy, all available response designations contributed to the BOR assessment. Tumor assessments are scheduled to be performed at Week 12 following randomization, every 8 weeks for the first 12 months and then every 12 weeks until disease progression

  2. Overall Survival (OS) Rate [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to October 2018, approximately 28 months ]
    OS is defined as the time between the date of randomization and the date of death due to any cause. A participant who has not died will be censored at the last known alive date. OS will be followed continuously while participants are on the study drug and every 3 months via in-person or phone contact after participants discontinue the study drug

  3. Median Overall Survival [ Time Frame: From date of randomization to date of death due to any cause (assessed up to April 2018, approximately 20 months) ]
    OS is defined as the time between the date of randomization and the date of death due to any cause. The results here do not account for any censoring of the data. OS will be followed continuously while participants are on the study drug and every 3 months via in-person or phone contact after participants discontinue the study drug

  4. Rate of Progression Free Survival (PFS) at 6 Months [ Time Frame: 6 months ]
    PFS is defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Participants who die without a reported progression will be considered to have progressed on the date of their death. Particpants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die will be censored on their date of randomization. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the initiation of subsequent anti-cancer therapy

  5. Median Progression Free Survival (PFS) [ Time Frame: Date of randomization to first date of documented progression or death due to any cause, whichever occurs first (assessed up to April 2017, approximately 12 months) ]
    PFS is defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Participants who die without a reported progression will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die will be censored on their date of randomization. Participants who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the initiation of subsequent anti-cancer therapy

  6. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Physical Functioning Scale [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 comprises 6 functional scales (role function, physical functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as nine symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). With the exception of 2 items included in the global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores for all functional scales and Global Health Status indicate better HRQoL; an increase from baseline indicates improvement in HRQoL compared to baseline.

  7. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Role Functioning Scale [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 comprises 6 functional scales (role function, physical functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as nine symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). With the exception of 2 items included in the global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores for all functional scales and Global Health Status indicate better HRQoL; an increase from baseline indicates improvement in HRQoL compared to baseline.

  8. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Emotional Functioning Scale [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 comprises 6 functional scales (role function, physical functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as nine symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). With the exception of 2 items included in the global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores for all functional scales and Global Health Status indicate better HRQoL; an increase from baseline indicates improvement in HRQoL compared to baseline.

  9. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Cognitive Functioning Scale [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 comprises 6 functional scales (role function, physical functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as nine symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). With the exception of 2 items included in the global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores for all functional scales and Global Health Status indicate better HRQoL; an increase from baseline indicates improvement in HRQoL compared to baseline.

  10. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Social Functioning Scale [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 comprises 6 functional scales (role function, physical functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as nine symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). With the exception of 2 items included in the global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores for all functional scales and Global Health Status indicate better HRQoL; an increase from baseline indicates improvement in HRQoL compared to baseline.

  11. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Global Health Status [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 comprises 6 functional scales (role function, physical functioning, cognitive functioning, emotional functioning, social functioning and global quality of life) as well as nine symptom scales (fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). With the exception of 2 items included in the global health/quality of life scale, for which responses range from 1 (Very poor) to 7 (Excellent), item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores for all functional scales and Global Health Status indicate better HRQoL; an increase from baseline indicates improvement in HRQoL compared to baseline.

  12. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Dyspnea [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The Dyspnea sub-scale item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores indicate a higher level of symptoms;lower scores indicating lesser burden and improved symptoms or quality of life. A clinically meaningful change in score may be regarded as 10 points.

  13. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Insomnia [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The Insomnia sub-scale item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores indicate a higher level of symptoms;lower scores indicating lesser burden and improved symptoms or quality of life. A clinically meaningful change in score may be regarded as 10 points.

  14. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Appetite Loss [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The Appetite loss sub-scale item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores indicate a higher level of symptoms;lower scores indicating lesser burden and improved symptoms or quality of life. A clinically meaningful change in score may be regarded as 10 points.

  15. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Constipation [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The Constipation sub-scale item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores indicate a higher level of symptoms;lower scores indicating lesser burden and improved symptoms or quality of life. A clinically meaningful change in score may be regarded as 10 points

  16. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Diarrhea [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The Diarrhea sub-scale item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores indicate a higher level of symptoms;lower scores indicating lesser burden and improved symptoms or quality of life. A clinically meaningful change in score may be regarded as 10 points.

  17. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Financial Difficulties [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The Financial difficulties sub-scale item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores indicate a higher level of symptoms;lower scores indicating lesser burden and improved symptoms or quality of life. A clinically meaningful change in score may be regarded as 10 points

  18. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Fatigue [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The Fatigue sub-scale item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores indicate a higher level of symptoms;lower scores indicating lesser burden and improved symptoms or quality of life. A clinically meaningful change in score may be regarded as 10 points

  19. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Nausea and Vomiting [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The Nausea and Vomiting sub-scale item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores indicate a higher level of symptoms;lower scores indicating lesser burden and improved symptoms or quality of life. A clinically meaningful change in score may be regarded as 10 points for the various scales of the EORTC QLQ-C30

  20. Mean Changes From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Pain [ Time Frame: Weeks 7, 16, 20, 24, 28, 32, 36, 40 ]
    Health Related Quality of Life (HRQoL) was assessed using the EORTC QLQ-C30 questionnaire. The Pain sub-scale item responses range from 1 (Not at all) to 4 (Very much). Raw scores for the EORTC QLQ-C30 are transformed to a 0-100 metric such that higher scores indicate a higher level of symptoms;lower scores indicating lesser burden and improved symptoms or quality of life. A clinically meaningful change in score may be regarded as 10 points



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Subject must have been diagnosed with stage III or/and stage IV histologically confirmed melanoma [per American Joint Committee on Cancer (AJCC) staging system] that is unresectable or metastatic
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Subject has not been treated by systemic anticancer therapy for unresectable or metastatic melanoma

Exclusion Criteria:

  • Subjects with active brain metastases or leptomeningeal metastases
  • Subjects with ocular melanoma
  • Subjects with active, known or suspected autoimmune disease

Other protocol defined inclusion/exclusion criteria could apply


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 ClinicalTrials.gov identifier (NCT number): NCT02714218


Locations
Show Show 57 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:
Study Protocol  [PDF] February 20, 2018
Statistical Analysis Plan  [PDF] October 30, 2018


Additional Information:
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02714218    
Other Study ID Numbers: CA209-511
First Posted: March 21, 2016    Key Record Dates
Results First Posted: April 23, 2019
Last Update Posted: October 1, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Nivolumab
Ipilimumab
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents, Immunological
Antineoplastic Agents