We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02905266




Registration number
NCT02905266
Ethics application status
Date submitted
14/09/2016
Date registered
19/09/2016
Date last updated
17/12/2020

Titles & IDs
Public title
A Safety and Efficacy Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Melanoma
Scientific title
Phase IIIb, Randomized, Study of Multiple Administration Regimens for Nivolumab Plus Ipilimumab in Subjects With Previously Untreated Unresectable or Metastatic Melanoma
Secondary ID [1] 0 0
2016-001941-26
Secondary ID [2] 0 0
CA209-742
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Nivolumab
Other interventions - Ipilimumab

Experimental: Nivolumab and Ipilimumab Concomitant Administration - Followed by Nivolumab monotherapy

Experimental: Nivolumab and Ipilimumab Sequential Administration - Followed by Nivolumab monotherapy


Other interventions: Nivolumab
-Specified dose on specified days

Other interventions: Ipilimumab
-Specified dose on specified days

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Within 2 days from administration of any of the 4 doses in part 1 period (approximately 12 weeks)
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
From initial dose of study treatment and within 30 days of the last dose of study treatment (approximately 25 months)
Secondary outcome [5] 0 0
Geometric Mean Concentration of Ipilimumab at End of Infusion (EOI)
Timepoint [5] 0 0
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.
Secondary outcome [6] 0 0
Geometric Mean Concentration of Nivolumab at End of Infusion (EOI)
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Geometric Mean Trough Concentration of Ipilimumab
Timepoint [7] 0 0
From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Secondary outcome [8] 0 0
Geometric Mean Trough Concentration of Nivolumab
Timepoint [8] 0 0
From Cycle 2, Day 1 to Cycle 4, Day 1 (approximately 6 weeks). Each cycle lasts 3 weeks.
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Week 12 following randomization, every 8 weeks for the first 12 months and then every 12 weeks until disease progression (approximately 20 months)
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
From the date of randomization to the first date of documented progression (approximately 26 months)

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



- 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Melanoma Institute Australia - North Sydney
Recruitment hospital [2] 0 0
Greenslopes Private Hospital - Greenslopes
Recruitment hospital [3] 0 0
Cabrini Hospital - Malvern
Recruitment postcode(s) [1] 0 0
- North Sydney
Recruitment postcode(s) [2] 0 0
- Greenslopes
Recruitment postcode(s) [3] 0 0
- Malvern
Recruitment outside Australia
Country [1] 0 0
France
State/province [1] 0 0
Lyon Cedex 08
Country [2] 0 0
France
State/province [2] 0 0
Marseille Cedex 5
Country [3] 0 0
France
State/province [3] 0 0
Nantes Cedex 1
Country [4] 0 0
France
State/province [4] 0 0
Paris Cedex 14
Country [5] 0 0
France
State/province [5] 0 0
Paris
Country [6] 0 0
France
State/province [6] 0 0
Tours
Country [7] 0 0
Italy
State/province [7] 0 0
Genova
Country [8] 0 0
Italy
State/province [8] 0 0
Meldola (FC)
Country [9] 0 0
Italy
State/province [9] 0 0
Milan
Country [10] 0 0
Italy
State/province [10] 0 0
Torino
Country [11] 0 0
Spain
State/province [11] 0 0
Barcelona
Country [12] 0 0
Spain
State/province [12] 0 0
Madrid
Country [13] 0 0
Spain
State/province [13] 0 0
Sevilla

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02905266
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications