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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01515189




Registration number
NCT01515189
Ethics application status
Date submitted
18/01/2012
Date registered
24/01/2012
Date last updated
31/07/2019

Titles & IDs
Public title
Phase 3 Trial in Subjects With Metastatic Melanoma Comparing 3 mg/kg Ipilimumab Versus 10 mg/kg Ipilimumab
Scientific title
A Randomized Double-Blind Phase III Study of Ipilimumab Administered at 3 mg/kg Versus at 10 mg /kg in Subjects With Previously Treated or Untreated Unresectable or Metastatic Melanoma
Secondary ID [1] 0 0
2011-004029-28
Secondary ID [2] 0 0
CA184-169
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 - Ipilimumab

Experimental: Arm 1: Ipilimumab (3 mg/kg) - Ipilimumab 3 mg/kg solution intravenously once every 3 weeks for 4 doses; option for Re-induction, until disease progression or unacceptable toxicity

Experimental: Arm 2: Ipilimumab (10 mg/kg) - Ipilimumab 10 mg/kg solution intravenously once every 3 weeks for 4 doses; option for Re-induction, until disease progression or unacceptable toxicity


Other interventions: Ipilimumab


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

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) - OS is defined for each participant as the time between randomization date and death due to any cause. The survival time for participants who had not died was censored at the last known alive date. Median and associated 2-sided 95% confidence intervals were calculated using the method of Brookmeyer and Crowley.
Timepoint [1] 0 0
Approximately 48 months (assessed up to February 2016)
Secondary outcome [1] 0 0
Progression Free Survival (PFS) by mWHO Criteria - PFS was defined as the time between randomization date and the date of progression or death, whichever occurred first. A participant who died without reported prior progression was considered to have progressed on the date of death. For a participant who underwent resection post randomization, PFS was censored on last tumor assessment date prior to resection. For those who remained alive and had not progressed, PFS was censored on last evaluable tumor assessment date. Participants who had not died and had no recorded post-baseline tumor assessment were censored at the day of randomization. For participants who had Progressive Disease (PD) prior to Week 12 and a subsequent assessment of Stable Disease (SD), Partial Response (PR), or Complete Response (CR), the date of PD following response was used in the analysis of PFS; otherwise these participants were censored on the date of their last tumor assessment. Median and 2-sided 95% CIs were calculated with Brookmeyer Crowley method.
Timepoint [1] 0 0
From date of randomization until 540 death events occurred (approximately 48 months)
Secondary outcome [2] 0 0
Best Overall Response Rate (BORR) by mWHO Criteria - BORR by treatment arm was defined as the total number of randomized participants in the arm whose BOR is CR or PR, divided by the total number of randomized participants in the arm. Any participant who was unevaluable for BOR, e.g. on account of missing or "not evaluable" assessments, was included in the denominator of the calculation (i.e. was considered a non-responder with respect to the BORR endpoint). 95% 2-sided exact confidence intervals were computed using the method of Clopper and Pearson.
Timepoint [2] 0 0
From date of randomization until 540 death events occurred (approximately 48 months)
Secondary outcome [3] 0 0
Disease Control Rate (DCR) by mWHO Criteria - DCR by treatment arm was defined as the total number of randomized participants in the arm whose BOR is CR, PR or SD, divided by the total number of randomized participants in the arm. Any participant who was unevaluable for Disease Control (DC), (e.g. on account of missing or "not evaluable" assessments), was included in the denominator of the calculation (i.e. was considered a non-responder with respect to the DCR endpoint). 95% 2-sided exact confidence intervals were computed using the Clopper and Pearson method.
Timepoint [3] 0 0
From date of randomization until 540 death events occurred (approximately 48 months)
Secondary outcome [4] 0 0
Duration of Response (DOR) by mWHO Criteria - Duration of response for participants whose BOR was CR or PR was defined as the time between the date measurement criteria were first met for overall response of PR or CR (whichever status was recorded first) and the date of disease progression or death (whichever occurred first). For participants who underwent tumor resection following response but prior to disease progression, duration of response was censored on the date of last evaluable tumor assessment prior to resection. For participants who had BOR of SD, PR or CR at Week 12, or a confirmed response of PR or CR before Week 12, the date of PD following thereafter (where available) was used in the analysis of duration of response. For those participants who remained alive and had not progressed following response, duration of response was censored on the date of last evaluable tumor assessment. Median and associated 2-sided 95% confidence intervals were calculated using the Brookmeyer Crowley method.
Timepoint [4] 0 0
From date of randomization until 540 death events occurred (approximately 48 months)
Secondary outcome [5] 0 0
Duration of Stable Disease by mWHO Criteria - Duration of stable disease was defined for participants whose BOR was SD as the time between when SD was first documented and the date of PD or death (whichever occurred first). For a participant who underwent tumor resection following Week 12 but prior to disease progression, duration of stable disease was censored on the date of the last evaluable tumor assessment prior to resection. For participants who had BOR of SD at Week 12, the date of PD following thereafter (where available) was used in the analysis of duration of stable disease. For participants with BOR of SD who had not subsequently progressed and who remained alive, duration of stable disease was censored on the date of last evaluable tumor assessment. Median and associated 2-sided 95% confidence intervals were calculated using the Brookmeyer and Crowley method.
Timepoint [5] 0 0
From date of randomization until 540 death events occurred (approximately 48 months)
Secondary outcome [6] 0 0
Rate of Overall Survival - OS is defined for each participant as the time between randomization date and death due to any cause. The survival time for participants who had not died was censored at the last known alive date. Survival rates were calculated based on Kaplan-Meier estimation with log-log transformed confidence intervals. The survival rate at x year(s) is defined as the probability that a subject is alive at x year(s) following randomization.
Timepoint [6] 0 0
Approximately 66 months
Secondary outcome [7] 0 0
Overall Survival of Participants With Brain Metastases at Baseline - OS for each participant with brain metastases at baseline was measured as the time between randomization date and death due to any cause. The survival time for participants who had not died was censored at the last known alive date. Median OS, and associated 2-sided 95% confidence intervals were calculated using the Brookmeyer and Crowley method.
Timepoint [7] 0 0
From date of randomization until 540 death events occurred (approximately 48 months)

Eligibility
Key inclusion criteria
For more information regarding BMS clinical trial participation, please visit
www.BMSStudyConnect.com.



- Unresectable Stage III or Stage IV melanoma

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Brain metastases with symptoms or requiring treatment

- History of autoimmune disease

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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,SA,VIC
Recruitment hospital [1] 0 0
Local Institution - Camperdown
Recruitment hospital [2] 0 0
Local Institution - Coffs Harbour
Recruitment hospital [3] 0 0
Local Institution - Brisbane
Recruitment hospital [4] 0 0
Local Institution - Southport
Recruitment hospital [5] 0 0
Local Institution - Adelaide
Recruitment hospital [6] 0 0
Local Institution - Heidelberg
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [3] 0 0
4102 - Brisbane
Recruitment postcode(s) [4] 0 0
4215 - Southport
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Argentina
State/province [9] 0 0
Tucuman
Country [10] 0 0
Argentina
State/province [10] 0 0
Buenos Aires
Country [11] 0 0
Austria
State/province [11] 0 0
Linz
Country [12] 0 0
Austria
State/province [12] 0 0
Vienna
Country [13] 0 0
Belgium
State/province [13] 0 0
Bruxelles
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Canada
State/province [15] 0 0
Alberta
Country [16] 0 0
Canada
State/province [16] 0 0
Nova Scotia
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
Czechia
State/province [18] 0 0
Brno
Country [19] 0 0
Czechia
State/province [19] 0 0
Olomouc
Country [20] 0 0
Czechia
State/province [20] 0 0
Praha 2
Country [21] 0 0
Denmark
State/province [21] 0 0
Aarhus
Country [22] 0 0
Denmark
State/province [22] 0 0
Herlev
Country [23] 0 0
Denmark
State/province [23] 0 0
Odense
Country [24] 0 0
France
State/province [24] 0 0
Bordeaux
Country [25] 0 0
France
State/province [25] 0 0
Dijon Cedex
Country [26] 0 0
France
State/province [26] 0 0
Grenoble
Country [27] 0 0
France
State/province [27] 0 0
Lille
Country [28] 0 0
France
State/province [28] 0 0
Marseille Cedex 5
Country [29] 0 0
France
State/province [29] 0 0
Nantes Cedex 1
Country [30] 0 0
France
State/province [30] 0 0
Paris
Country [31] 0 0
France
State/province [31] 0 0
Pierre Benite
Country [32] 0 0
France
State/province [32] 0 0
Reims Cedex
Country [33] 0 0
France
State/province [33] 0 0
Toulouse
Country [34] 0 0
France
State/province [34] 0 0
Villejuif
Country [35] 0 0
Germany
State/province [35] 0 0
Buxtehude
Country [36] 0 0
Germany
State/province [36] 0 0
Essen
Country [37] 0 0
Germany
State/province [37] 0 0
Hannover
Country [38] 0 0
Germany
State/province [38] 0 0
Heidelberg
Country [39] 0 0
Germany
State/province [39] 0 0
Kiel
Country [40] 0 0
Germany
State/province [40] 0 0
Mainz
Country [41] 0 0
Germany
State/province [41] 0 0
Munich
Country [42] 0 0
Germany
State/province [42] 0 0
Tubingen
Country [43] 0 0
Hungary
State/province [43] 0 0
Budapest
Country [44] 0 0
Hungary
State/province [44] 0 0
Kaposvar
Country [45] 0 0
Hungary
State/province [45] 0 0
Szeged
Country [46] 0 0
Israel
State/province [46] 0 0
Jerusalem
Country [47] 0 0
Italy
State/province [47] 0 0
Meldola (fc)
Country [48] 0 0
Italy
State/province [48] 0 0
Milano
Country [49] 0 0
Italy
State/province [49] 0 0
Napoli
Country [50] 0 0
Italy
State/province [50] 0 0
Padova
Country [51] 0 0
Italy
State/province [51] 0 0
Roma
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Italy
State/province [52] 0 0
Siena
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Mexico
State/province [53] 0 0
Guanajuato
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Netherlands
State/province [54] 0 0
Amsterdam
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Netherlands
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Groningen
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Netherlands
State/province [56] 0 0
Leiden
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Norway
State/province [57] 0 0
Bergen
Country [58] 0 0
Norway
State/province [58] 0 0
Oslo
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Poland
State/province [59] 0 0
Gdansk
Country [60] 0 0
Poland
State/province [60] 0 0
Poznan
Country [61] 0 0
Poland
State/province [61] 0 0
Warszawa
Country [62] 0 0
South Africa
State/province [62] 0 0
Western CAPE
Country [63] 0 0
Spain
State/province [63] 0 0
Barcelona
Country [64] 0 0
Spain
State/province [64] 0 0
Madrid
Country [65] 0 0
Spain
State/province [65] 0 0
Navarra
Country [66] 0 0
Spain
State/province [66] 0 0
Valencia
Country [67] 0 0
Sweden
State/province [67] 0 0
Gothenberg
Country [68] 0 0
Sweden
State/province [68] 0 0
Lund
Country [69] 0 0
Sweden
State/province [69] 0 0
Stockholm
Country [70] 0 0
Sweden
State/province [70] 0 0
Umea
Country [71] 0 0
Switzerland
State/province [71] 0 0
Lausanne
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Greater Manchester
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Strathclyde
Country [74] 0 0
United Kingdom
State/province [74] 0 0
London
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Swansea

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine whether giving Ipilimumab at a dose of 10mg/kg will
extend the lives of subjects with unresectable or metastatic melanoma more than giving
Ipilimumab at a dose of 3 mg/kg
Trial website
https://clinicaltrials.gov/show/NCT01515189
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