Dacarbazine and Ipilimumab vs. Dacarbazine With Placebo in Untreated Unresectable Stage III or IV Melanoma

NCT00324155 | Completed Phase 3 Results DMC

• 1 other identifier: CA184-024
• Study Type: interventional
• Target: 681
• Locations: 24 countries
• Sites: 122

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

Conditions

Melanoma

Keywords

Stage IIIc N3 (unresectable); Stage IV melanoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS was defined as the time from the date of randomization until the date of death. Analysis of OS was to be done once 416 deaths had occurred (primary endpoint). However, analysis occurred at 414 deaths (February 7, 2011), due to operational timing of the study. Median number of months of OS and associated confidence interval calculated using the method of Brookmeyer and Crowley.

  Date of randomization to 37 months through 5-year follow-up and up to approximately 76 months

Secondary Outcomes (12)

• Survival Rate at 1 Year, 18 Months, 2 Years, and 3 Years

  Date of randomization to 3 years following randomization

• Disease Control Rate (DCR)

  First dose to last tumor assessment prior to subsequent therapy at data cutoff for Primary Endpoint (approximately 5 years)

• Median Number of Months of Progression-free Survival (PFS)

  Randomization to date of progression or death to approximately 5 years

• Progression-free Survival (PFS) Rate Truncated at Week 12

  Day 78

• Best Overall Response Rate (BORR)

  First dose to last tumor assessment at data cutoff for primary endpoint (approximately 5 years)

Study Arms (2)

Arm A: Ipilimumab and Dacarbazine

EXPERIMENTAL

In Maintenance phase: Ipilimumab will be continued. Dacarbazine was given up to Week 22 and is not given in the Maintenance phase

Drug: Ipilimumab; Drug: Dacarbazine

Arm B: Placebo and Dacarbazine

ACTIVE COMPARATOR

Drug: Placebo; Drug: Dacarbazine

Interventions

Ipilimumab DRUG

Intravenous solution; intravenous; 10mg/kg; one dose every 3 weeks for 10 weeks then one dose every 12 weeks starting at Week 24, until disease progression, unacceptable toxicity or withdrawal of consent In Maintenance phase: Only Ipilimumab: 10mg/kg, every 12 weeks will be continued until disease progression

Also known as: MDX-010, BMS-734016

Arm A: Ipilimumab and Dacarbazine

Placebo DRUG

Intravenous solution; intravenous; 0 mg; one dose every 3 weeks for 10 weeks then one dose every 12 weeks starting at Week 24; until disease progression, unacceptable toxicity or withdrawal of consent

Arm B: Placebo and Dacarbazine

Dacarbazine DRUG

Intravenous solution; intravenous; 850 mg/m\^2; one dose every 3 weeks for 22 weeks, until disease progression, unacceptable toxicity or withdrawal of consent

Arm A: Ipilimumab and Dacarbazine; Arm B: Placebo and Dacarbazine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Medarex: collaborator

Study Sites (127)

Pacific Cancer Medical Center

Anaheim, California, 92801, United States

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Wilshire Oncology Medical Group Inc

La Verne, California, 91750, United States

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The Angeles Clinic And Research Institute

Los Angeles, California, 90025, United States

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Comprehensive Cancer Center

Palm Springs, California, 92262, United States

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Sharp Clinical Oncology Research

San Diego, California, 92123, United States

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Saint Francis Hospital And Medical Center

Hartford, Connecticut, 06105, United States

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Hematology Oncology, P.C.

Stamford, Connecticut, 06902-3628, United States

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Cancer Specialists Of North Florida Beaches

Jacksonville, Florida, 32256, United States

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Orlando Health, Inc. M.D. Anderson Cancer Center Orlando

Orlando, Florida, 32806, United States

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Hematology Oncology Associates Of The Treasure Coast

Port Saint Lucie, Florida, 34952, United States

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University Of Chicago

Chicago, Illinois, 60637, United States

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Mid-Illinois Hematology/Oncology Associates, Ltd.

Normal, Illinois, 61761, United States

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Oncology Specialists, Sc

Park Ridge, Illinois, 60068, United States

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Central Indiana Cancer Centers

Fishers, Indiana, 46037, United States

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Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

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Hutchinson Clinic, Pa

Hutchinson, Kansas, 67502, United States

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Kentucky Cancer Clinic

Hazard, Kentucky, 41701, United States

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Greater Baltimore Medical Center

Baltimore, Maryland, 21204, United States

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Sinai Hospital Of Baltimore

Baltimore, Maryland, 21215, United States

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Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

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Ellis Fischel Cancer Center

Columbia, Missouri, 65203, United States

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St Joseph Oncology Inc

Saint Joseph, Missouri, 64507, United States

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University Of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

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Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

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Blumenthal Cancer Center

Charlotte, North Carolina, 28204, United States

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Providence Portland Medical Center

Portland, Oregon, 97213, United States

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St. Luke'S Hospital & Health Network

Bethlehem, Pennsylvania, 18015, United States

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Lowcountry Hematology & Oncology, Pa

Mt. Pleasant, South Carolina, 29464, United States

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Thompson Cancer Survival Center

Knoxville, Tennessee, 37916, United States

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Vanderbilt-Ingram Cancer Ctr

Nashville, Tennessee, 37232, United States

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Joe Arrington Cancer Research And Treatment Center

Lubbock, Texas, 79410, United States

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Virginia Cancer Institute

Richmond, Virginia, 23226, United States

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Local Institution

Buenos Aires, Buenos Aires, 1185, Argentina

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Buenos Aires, Buenos Aires, C1408INH, Argentina

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Buenos Aires, Buenos Aires, C1426ANZ, Argentina

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Córdoba, Córdoba Province, X5000AAI, Argentina

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Santa Fe, Santa Fe Province, S3000FFU, Argentina

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Coffs Harbour, New South Wales, 2450, Australia

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Newcastle, New South Wales, 2300, Australia

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Port Macquarie, New South Wales, 2444, Australia

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South Brisbane, Queensland, 4101, Australia

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Box Hill, Victoria, 3128, Australia

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Vienna, 1090, Austria

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Brasschaat, 2930, Belgium

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Brussels, 1200, Belgium

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Edegem, B-2650, Belgium

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Ghent, 9000, Belgium

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Fortaleza, Ceará, 60430-230, Brazil

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Porto Alegre, Rio Grande do Sul, 90050-170, Brazil

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Porto Alegre, Rs, Rio Grande do Sul, 90610-000, Brazil

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São Paulo, São Paulo, 01508-010, Brazil

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Edmonton, Alberta, T6G 1Z2, Canada

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Montreal, Quebec, H1T 2W4, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Saskatoon, Saskatchewan, S7N 4H4, Canada

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Santiago, Chile

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Olomouc, 775 20, Czechia

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Prague, 128 08, Czechia

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Nantes, Cedex 1, 44093, France

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Saint-Etienne, Cedex 2, 42055, France

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Brest, Cedex, 29200, France

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Bordeaux, 33075, France

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Marseille, 13009, France

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Paris, 75010, France

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Pierre-Bénite, 69495, France

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Villejuif, 94805, France

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Berlin, 12200, Germany

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Heidelberg, 69120, Germany

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Jena, 07740, Germany

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Kiel, 24105, Germany

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Mannheim, 68167, Germany

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München, 81675, Germany

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Tübingen, 72076, Germany

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Kaposyar, 7400, Hungary

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Dublin, Dublin 4, Ireland

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Galway, Galway, Ireland

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Cork, Ireland

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Jerusalem, 91120, Israel

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Tel Aviv, 64239, Israel

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Genova, 16128, Italy

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Milan, 20141, Italy

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Napoli, 80131, Italy

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Padua, 35128, Italy

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Ragusa, 97100, Italy

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Rome, 00144, Italy

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Siena, 53100, Italy

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Eindhoven, 5623 EJ, Netherlands

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Hv Amsterdam, 1081, Netherlands

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Wurzburg, 97080, Netherlands

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Montebello, Oslo County, 0310, Norway

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Gdansk, 80-219, Poland

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Lodz, 93-509, Poland

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Lublin, 20-090, Poland

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Poznan, 61-866, Poland

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Wroclaw, 51-124, Poland

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Lisbon, 1099-023, Portugal

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Pyatigorsk, Stavropol Kray, 357502, Russia

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Moscow, 105229, Russia

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Moscow, 115478, Russia

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Murmansk, 183047, Russia

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Ryazan, 390011, Russia

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Saint Petersburg, 191104, Russia

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Saint Petersburg, 198255, Russia

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Samara, 443066, Russia

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Stavropol, 355047, Russia

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Port Elizabeth, Eastern Cape, 6000, South Africa

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Groenkloof, Gauteng, 0181, South Africa

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Pretoria, Gauteng, 0041, South Africa

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Saxonworld, Gauteng, 2196, South Africa

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Cape Town, Western Cape, 7570, South Africa

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Johannesburg, 2199, South Africa

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Barcelona, 08036, Spain

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Canarias, 38320, Spain

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Valencia, 46014, Spain

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Zaragoza, 50009, Spain

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Basel, CH-4031, Switzerland

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Geneva, 1211, Switzerland

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Cherkassy, 18009, Ukraine

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Dnipro, 49044, Ukraine

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Lviv, 79031, Ukraine

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Uzhhorod, 88000, Ukraine

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Bristol, Avon, BS2 8ED, United Kingdom

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Poole, Dorset, BH15 2JB, United Kingdom

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Chelmsford, Essex, CM1 7ET, United Kingdom

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London, Greater London, SW3 6JJ, United Kingdom

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Metropolitan Borough of Wirral, Merseyside, CH63 3JY, United Kingdom

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Guildford, Surrey, GU2 7XX, United Kingdom

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Related Publications (3)

• 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.

  PMID: 25713437 DERIVED

• 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.

  PMID: 25667295 DERIVED

• 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.

  PMID: 21639810 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; Dacarbazine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2006
• First Posted: May 10, 2006
• Study Start: August 1, 2006
• Primary Completion: January 1, 2011
• Study Completion: October 1, 2013
• Last Updated: November 3, 2014
• Results First Posted: March 10, 2014

Record last verified: 2014-10

Locations

CZ (2); CL (1); IE (3); PT (1); AU (1); RU (9); UA (4); GB (6); IT (7); PL (5); HU (1); BE (4); CA (4); ZA (6); DE (7); BR (4); AR (5); NO (1); ES (4); US (32); NL (3); IL (2); CH (2); FR (8)