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A Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Melanoma

Primary Purpose

Melanoma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Nivolumab
Ipilimumab
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma

Eligibility Criteria

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

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

Inclusion Criteria:

  • Males and Females, ages 15 years ≥ of age (Except where local regulations and/or institutional policies do not allow for subjects < 18 years of age to participate)
  • Subjects must have been diagnosed with stage III or/and stage IV histologically confirmed melanoma that is unresectable or metastatic
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Subjects have 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

Sites / Locations

  • Melanoma Institute Australia
  • Greenslopes Private Hospital
  • Cabrini Hospital
  • Local Institution
  • Hopital De La Timone
  • Local Institution
  • Local Institution
  • Hopital Saint Louis
  • Hopital Trousseau - Chru Tours
  • Istituto Nazionale Per La Ricerca Sul Cancro - Oncologia Med
  • Istituto Scientifico Romagnolo Per Lo Studio E Cura Tumori
  • Istituto Europeo Di Oncologia
  • Azienda Ospedaliera Citta della Salute e della Scienza
  • Local Institution
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Nivolumab and Ipilimumab Concomitant Administration

Nivolumab and Ipilimumab Sequential Administration

Arm Description

Followed by Nivolumab monotherapy

Followed by Nivolumab monotherapy

Outcomes

Primary Outcome Measures

Percentage of Participants Affected by Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ)
This outcome describes the percentage of participants experiencing at least 1 AE in the MedDRA Anaphylactic Reaction broad scope SMQ. Such AEs include any acute systemic reaction characterized by a large list of terms, including (but not limited to) pruritus, urticaria, flushing, hypotension, respiratory distress, and vascular insufficiency. It also includes other signs and symptoms such as asthma, choking sensation, coughing, sneezing, and difficulty breathing due to laryngeal spasm and/or bronchospasm. Less frequent clinical presentations are also captured and include hyperventilation, sensation of foreign body, and ocular edema.

Secondary Outcome Measures

Percentage of Participants Affected by AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ
This outcome describes the percentage of participants experiencing at least 1 AE in the MedDRA Anaphylactic Reaction narrow scope SMQ. The narrow scope SMQ is composed of a large list of terms, including (but not limited to) anaphylactic shock and reaction, shock and shock symptoms, and circulatory collapse, among the others.
Percentage of Participants Affected by Hypersensitivity/Infusion Reaction Select AEs
This outcome describes the percentage of participants experiencing at least 1 AE in the Hypersensitivity/Infusion select AEs category. The select AEs consist of a list of preferred terms defined by the Sponsor and represent AEs with a potential immune-mediated etiology. The following 5 MedDRA preferred terms are included in the hypersensitivity/infusion reaction select AE category: Anaphylactic Reaction, Anaphylactic Shock, Bronchospasm, Hypersensitivity, and Infusion Related Reaction
Percentage of Participants Affected by All Causality Grade 3 - 5 AEs
This outcome describes the percentage of participants who experienced at least 1 AE of Grade 3 or higher defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria
Percentage of Participants Affected by Drug-related Grade 3 - 5 AEs
This outcome describes the percentage of participants who experienced at least 1 Drug-related AE of Grade 3 or higher defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria
Geometric Mean Concentration of Ipilimumab at End of Infusion (EOI)
Geometric Mean Concentration of Nivolumab at End of Infusion (EOI)
Geometric Mean Trough Concentration of Ipilimumab
Geometric Mean Trough Concentration of Nivolumab
Objective Response Rate (ORR)
The ORR is defined as the proportion of participants with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). The BOR is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of subsequent anti-cancer therapy, whichever occurs first.
Progression Free Survival (PFS)
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.

Full Information

First Posted
September 14, 2016
Last Updated
November 19, 2020
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT02905266
Brief Title
A Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Melanoma
Official Title
Phase IIIb, Randomized, Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Previously Untreated Unresectable or Metastatic Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
October 27, 2016 (Actual)
Primary Completion Date
October 23, 2017 (Actual)
Study Completion Date
October 25, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
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
No

5. Study Description

Brief Summary
This is a safety and efficacy study of different administration regimens of nivolumab plus Ipilimumab in subjects with previously untreated, unresectable or metastatic melanoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
106 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nivolumab and Ipilimumab Concomitant Administration
Arm Type
Experimental
Arm Description
Followed by Nivolumab monotherapy
Arm Title
Nivolumab and Ipilimumab Sequential Administration
Arm Type
Experimental
Arm Description
Followed by Nivolumab monotherapy
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Intervention Description
-Specified dose on specified days
Intervention Type
Biological
Intervention Name(s)
Ipilimumab
Intervention Description
-Specified dose on specified days
Primary Outcome Measure Information:
Title
Percentage of Participants Affected by Adverse Events (AEs) in the Broad Scope MedDRA Anaphylactic Reaction Standardized MedDRA Queries (SMQ)
Description
This outcome describes the percentage of participants experiencing at least 1 AE in the MedDRA Anaphylactic Reaction broad scope SMQ. Such AEs include any acute systemic reaction characterized by a large list of terms, including (but not limited to) pruritus, urticaria, flushing, hypotension, respiratory distress, and vascular insufficiency. It also includes other signs and symptoms such as asthma, choking sensation, coughing, sneezing, and difficulty breathing due to laryngeal spasm and/or bronchospasm. Less frequent clinical presentations are also captured and include hyperventilation, sensation of foreign body, and ocular edema.
Time Frame
Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)
Secondary Outcome Measure Information:
Title
Percentage of Participants Affected by AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ
Description
This outcome describes the percentage of participants experiencing at least 1 AE in the MedDRA Anaphylactic Reaction narrow scope SMQ. The narrow scope SMQ is composed of a large list of terms, including (but not limited to) anaphylactic shock and reaction, shock and shock symptoms, and circulatory collapse, among the others.
Time Frame
Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)
Title
Percentage of Participants Affected by Hypersensitivity/Infusion Reaction Select AEs
Description
This outcome describes the percentage of participants experiencing at least 1 AE in the Hypersensitivity/Infusion select AEs category. The select AEs consist of a list of preferred terms defined by the Sponsor and represent AEs with a potential immune-mediated etiology. The following 5 MedDRA preferred terms are included in the hypersensitivity/infusion reaction select AE category: Anaphylactic Reaction, Anaphylactic Shock, Bronchospasm, Hypersensitivity, and Infusion Related Reaction
Time Frame
Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)
Title
Percentage of Participants Affected by All Causality Grade 3 - 5 AEs
Description
This outcome describes the percentage of participants who experienced at least 1 AE of Grade 3 or higher defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria
Time Frame
From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)
Title
Percentage of Participants Affected by Drug-related Grade 3 - 5 AEs
Description
This outcome describes the percentage of participants who experienced at least 1 Drug-related AE of Grade 3 or higher defined using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria
Time Frame
From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)
Title
Geometric Mean Concentration of Ipilimumab at End of Infusion (EOI)
Time Frame
From Cycle 1, Day 1 to Cycle 4, Day 1 (approximately 9 weeks). Each cycle lasts 3 weeks. Cycle 1 day 1, Cycle 2 day 1 and Cycle 4 day 1 values reported.
Title
Geometric Mean Concentration of Nivolumab at End of Infusion (EOI)
Time Frame
From Cycle 1, Day 1 to Cycle 4, Day 1 (approximately 9 weeks). Each cycle lasts 3 weeks. Cycle 1 day 1, Cycle 2 day 1 and Cycle 4 day 1 values reported
Title
Geometric Mean Trough Concentration of Ipilimumab
Time Frame
From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Title
Geometric Mean Trough Concentration of Nivolumab
Time Frame
From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Title
Objective Response Rate (ORR)
Description
The ORR is defined as the proportion of participants with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). The BOR is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of subsequent anti-cancer therapy, whichever occurs first.
Time Frame
Week 12 following randomization, every 8 weeks for the first 12 months and then every 12 weeks until disease progression (approximately 20 months)
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
From the date of randomization to the first date of documented progression (approximately 26 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Males and Females, ages 15 years ≥ of age (Except where local regulations and/or institutional policies do not allow for subjects < 18 years of age to participate) Subjects must have been diagnosed with stage III or/and stage IV histologically confirmed melanoma that is unresectable or metastatic Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Subjects have 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Melanoma Institute Australia
City
North Sydney
State/Province
New South Wales
Country
Australia
Facility Name
Greenslopes Private Hospital
City
Greenslopes
State/Province
Queensland
Country
Australia
Facility Name
Cabrini Hospital
City
Malvern
State/Province
Victoria
Country
Australia
Facility Name
Local Institution
City
Lyon Cedex 08
ZIP/Postal Code
69373
Country
France
Facility Name
Hopital De La Timone
City
Marseille Cedex 5
ZIP/Postal Code
13385
Country
France
Facility Name
Local Institution
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
Local Institution
City
Paris Cedex 14
ZIP/Postal Code
75679
Country
France
Facility Name
Hopital Saint Louis
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
Hopital Trousseau - Chru Tours
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Istituto Nazionale Per La Ricerca Sul Cancro - Oncologia Med
City
Genova
ZIP/Postal Code
16128
Country
Italy
Facility Name
Istituto Scientifico Romagnolo Per Lo Studio E Cura Tumori
City
Meldola (FC)
ZIP/Postal Code
47014
Country
Italy
Facility Name
Istituto Europeo Di Oncologia
City
Milan
ZIP/Postal Code
20141
Country
Italy
Facility Name
Azienda Ospedaliera Citta della Salute e della Scienza
City
Torino
ZIP/Postal Code
10137
Country
Italy
Facility Name
Local Institution
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Local Institution
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Local Institution
City
Sevilla
ZIP/Postal Code
41071
Country
Spain

12. IPD Sharing Statement

Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls

Learn more about this trial

A Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Melanoma

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