Clinical trial NCT00324155: Dacarbazine and Ipilimumab vs. Dacarbazine With Placebo in Untreated Unresectable Stage III or IV Melanoma
Official title: A Multi-center, Randomized, Double-Blind, Two-Arm, Phase III Study in Patients With Untreated Stage III (Unresectable) or IV Melanoma Receiving Dacarbazine Plus 10 mg/kg Ipilimumab (MDX-010) vs. Dacarbazine With Placebo
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Melanoma
Keywords: Stage IIIc N3 (unresectable)
Stage IV melanoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Medarex
First posted: 2006-05-10
Enrollment: 681
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical research study is to examine the safety and effectiveness (how well the drug works) of two different treatments for patients with melanoma. One treatment is an investigational compound (a drug that is not currently approved by the United States Food and Drug Administration \[FDA\]), know as Ipilimumab (also known as MDX-010 or BMS-734016) together with an approved chemotherapy drug called Dacarbazine

Detailed description: For the extension phase:

Allocation: single arm study; Masking: open label; Intervention Model: Single Group

Eligibility criteria: Inclusion Criteria:

* Informed Consent
* Measurable Disease
* Eastern Cooperative Oncology Group (ECOG) 0 or 1
* Lab / imaging requirements
* Neg for Human Immunodeficiency Virus (HIV), Hepatitis B (HepB), C
* Men and Women \> 18 years (16 were allowable)
* Prior therapy restriction (adjuvant only)

Exclusion:

* Pregnant / nursing
* Inadequate contraception
* Brain metastasis
* Primary ocular or mucosal melanoma

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Date of randomization to 37 months through 5-year follow-up and up to approximately 76 months
Secondary outcomes:
measure: Survival Rate at 1 Year, 18 Months, 2 Years, and 3 Years
timeFrame: Date of randomization to 3 years following randomization
measure: Disease Control Rate (DCR)
timeFrame: First dose to last tumor assessment prior to subsequent therapy at data cutoff for Primary Endpoint (approximately 5 years)
measure: Median Number of Months of Progression-free Survival (PFS)
timeFrame: Randomization to date of progression or death to approximately 5 years
measure: Progression-free Survival (PFS) Rate Truncated at Week 12
timeFrame: Day 78
measure: Best Overall Response Rate (BORR)
timeFrame: First dose to last tumor assessment at data cutoff for primary endpoint (approximately 5 years)
measure: Duration of Response (DOR): Randomized Participants With Response of Complete Response (CR) or Partial Response (PR)
timeFrame: Day of CR or PR to day of PD or death up to data cutoff for primary endpoint (approximately 5 years)
measure: Time to Response: All Randomized Participants With Response to Treatment
timeFrame: First dose to date of BOR up to data cutoff for primary endpoint (approximately 5 years)
measure: Duration of Stable Disease (SD): Randomized Participants With Stable Disease
timeFrame: Week 12 to date of disease progression or death up to data cutoff for primary endpoint (approximately 5 years)
measure: Percentage of Participants With Brain Metastasis-Free Survival at Time of Data Cutoff
timeFrame: Date of randomization up to data cutoff for primary endpoint (approximately 5 years)
measure: Number of Participants With Adverse Events (AEs), Drug-related AEs, AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Hypersensitivity, Immune-related AEs/SAEs, and Inflammatory AEs/SAEs
timeFrame: Week 1 (First Dose) to 70 days after last dose of study up to data cutoff for primary endpoint (approximately 5 years)
measure: Number of Participants With Grade 2-3 and Grade 3-4 Immune-related Adverse Events (irAEs) With Resolution Resolved
timeFrame: Week 1 (first dose) to 70 days after last dose up to data cutoff for primary endpoint (approximately 5 years)
measure: Time to Resolution of Grade 2-3, Grade 3-4 Immune-related Adverse Events (irAEs)
timeFrame: Week 1 (first dose) to 70 days after last dose up to database lock for primary endpoint (approximately 5 years)
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center
state: California
city: La Verne
country: United States
facility: Wilshire Oncology Medical Group Inc
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic And Research Institute
state: California
city: Palm Springs
country: United States
facility: Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: Sharp Clinical Oncology Research
state: California
city: Hartford
country: United States
facility: Saint Francis Hospital And Medical Center
state: Connecticut
city: Stamford
country: United States
facility: Hematology Oncology, P.C.
state: Connecticut
city: Jacksonville
country: United States
facility: Cancer Specialists Of North Florida Beaches
state: Florida
city: Orlando
country: United States
facility: Orlando Health, Inc. M.D. Anderson Cancer Center Orlando
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates Of The Treasure Coast
state: Florida
city: Chicago
country: United States
facility: University Of Chicago
state: Illinois
city: Normal
country: United States
facility: Mid-Illinois Hematology/Oncology Associates, Ltd.
state: Illinois
city: Park Ridge
country: United States
facility: Oncology Specialists, Sc
state: Illinois
city: Fishers
country: United States
facility: Central Indiana Cancer Centers
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Hutchinson
country: United States
facility: Hutchinson Clinic, Pa
state: Kansas
city: Hazard
country: United States
facility: Kentucky Cancer Clinic
state: Kentucky
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Sinai Hospital Of Baltimore
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center
state: Missouri
city: Saint Joseph
country: United States
facility: St Joseph Oncology Inc
state: Missouri
city: Albuquerque
country: United States
facility: University Of New Mexico Cancer Center
state: New Mexico
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Blumenthal Cancer Center
state: North Carolina
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke'S Hospital & Health Network
state: Pennsylvania
city: Mount Pleasant
country: United States
facility: Lowcountry Hematology & Oncology, Pa
state: South Carolina
city: Knoxville
country: United States
facility: Thompson Cancer Survival Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Ctr
state: Tennessee
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research And Treatment Center
state: Texas
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Cordoba
country: Argentina
facility: Local Institution
city: Santa Fe
country: Argentina
facility: Local Institution
city: Coffs Harbour
country: Australia
facility: Local Institution
state: New South Wales
city: Newcastle
country: Australia
facility: Local Institution
state: New South Wales
city: Port Macquarie
country: Australia
facility: Local Institution
state: New South Wales
city: South Brisbane
country: Australia
facility: Local Institution
state: Queensland
city: Box Hill
country: Australia
facility: Local Institution
state: Victoria
city: Vienna
country: Austria
facility: Local Institution
city: Brasschaat
country: Belgium
facility: Local Institution
city: Brussels
country: Belgium
facility: Local Institution
city: Edegem
country: Belgium
facility: Local Institution
city: Gent
country: Belgium
facility: Local Institution
city: Fortaleza
country: Brazil
facility: Local Institution
state: Ceara
city: Porto Alegre, Rs
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Saskatoon
country: Canada
facility: Local Institution
state: Saskatchewan
city: Santiago
country: Chile
facility: Local Institution
city: Olomouc
country: Czech Republic
facility: Local Institution
city: Praha
country: Czech Republic
facility: Local Institution
city: Nantes
country: France
facility: Local Institution
state: Cedex 1
city: Saint Etienne
country: France
facility: Local Institution
state: Cedex 2
city: Brest
country: France
facility: Local Institution
state: Cedex
city: Bordeaux
country: France
facility: Local Institution
city: Marseille
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Pierre Benite
country: France
facility: Local Institution
city: Villejuif
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Heidelberg
country: Germany
facility: Local Institution
city: Jena
country: Germany
facility: Local Institution
city: Kiel
country: Germany
facility: Local Institution
city: Mannheim
country: Germany
facility: Local Institution
city: Muenchen
country: Germany
facility: Local Institution
city: Tubingen
country: Germany
facility: Local Institution
city: Kaposyar
country: Hungary
facility: Local Institution
city: Dublin
country: Ireland
facility: Local Institution
state: Dublin 4
city: Cork
country: Ireland
facility: Local Institution
city: Galway
country: Ireland
facility: Local Institution
city: Jerusalem
country: Israel
facility: Local Institution
city: Tel Aviv
country: Israel
facility: Local Institution
city: Genova
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Napoli
country: Italy
facility: Local Institution
city: Padova
country: Italy
facility: Local Institution
city: Ragusa
country: Italy
facility: Local Institution
city: Rome
country: Italy
facility: Local Institution
city: Siena
country: Italy
facility: Local Institution
city: Eindhoven
country: Netherlands
facility: Local Institution
city: Hv Amsterdam
country: Netherlands
facility: Local Institution
city: Wurzburg
country: Netherlands
facility: Local Institution
city: Montebello
country: Norway
facility: Local Institution
state: Oslo
city: Gdansk
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Lublin
country: Poland
facility: Local Institution
city: Poznan
country: Poland
facility: Local Institution
city: Wroclaw
country: Poland
facility: Local Institution
city: Lisboa
country: Portugal
facility: Local Institution
city: Pyatigorsk
country: Russian Federation
facility: Local Institution
state: Stavropol
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Murmansk
country: Russian Federation
facility: Local Institution
city: Ryazan
country: Russian Federation
facility: Local Institution
city: Samara
country: Russian Federation
facility: Local Institution
city: St Petersburg
country: Russian Federation
facility: Local Institution
city: St.-Petersburg
country: Russian Federation
facility: Local Institution
city: Stavropol
country: Russian Federation
facility: Local Institution
city: Port Elizabeth
country: South Africa
facility: Local Institution
state: Eastern Cape
city: Groenkloof
country: South Africa
facility: Local Institution
state: Gauteng
city: Pretoria
country: South Africa
facility: Local Institution
state: Gauteng
city: Saxonworld
country: South Africa
facility: Local Institution
state: Gauteng
city: Cape Town
country: South Africa
facility: Local Institution
state: Western Cape
city: Johannesburg
country: South Africa
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Canarias
country: Spain
facility: Local Institution
city: Valencia
country: Spain
facility: Local Institution
city: Zaragoza
country: Spain
facility: Local Institution
city: Basel
country: Switzerland
facility: Local Institution
city: Geneva
country: Switzerland
facility: Local Institution
city: Cherkassy
country: Ukraine
facility: Local Institution
city: Dnepropetrovsk
country: Ukraine
facility: Local Institution
city: Lviv
country: Ukraine
facility: Local Institution
city: Uzhgorod
country: Ukraine
facility: Local Institution
city: Bristol
country: United Kingdom
facility: Local Institution
state: Avon
city: Poole
country: United Kingdom
facility: Local Institution
state: Dorset
city: Chelmsford
country: United Kingdom
facility: Local Institution
state: Essex
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: Wirral
country: United Kingdom
facility: Local Institution
state: Merseyside
city: Guildford
country: United Kingdom
facility: Local Institution
state: Surrey
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Maio M, Grob JJ, Aamdal S, Bondarenko I, Robert C, Thomas L, Garbe C, Chiarion-Sileni V, Testori A, Chen TT, Tschaika M, Wolchok JD. Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial. J Clin Oncol. 2015 Apr 1;33(10):1191-6. doi: 10.1200/JCO.2014.56.6018. Epub 2015 Feb 23.
citation: Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, Patt D, Chen TT, Berman DM, Wolchok JD. Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma. J Clin Oncol. 2015 Jun 10;33(17):1889-94. doi: 10.1200/JCO.2014.56.2736. Epub 2015 Feb 9.
citation: Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH Jr, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen TT, Humphrey R, Hoos A, Wolchok JD. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011 Jun 30;364(26):2517-26. doi: 10.1056/NEJMoa1104621. Epub 2011 Jun 5.