A Treatment Combination for Patients With Unresectable Stage III or Stage IV Melanoma

This study has been completed.
Sponsor:
Collaborator:
Onyx Pharmaceuticals
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00111007
First received: May 16, 2005
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

The objectives of this study are to compare the anti-tumor activity as measured by Progression Free Survival (PFS) and tolerability of Sorafenib in combination with Paclitaxel and Carboplatin versus Paclitaxel and Carboplatin in combination with placebo in subjects with unresectable Stage III or Stage IV melanoma who progressed after receiving only one prior therapy containing Dacarbazine (DTIC) or Temozolomide (TMZ).


Condition Intervention Phase
Melanoma
Drug: Sorafenib (Nexavar, BAY43-9006)
Drug: Carboplatin/Paclitaxel
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase III Randomized, Placebo Controlled Study of Sorafenib in Repeated Cycles of 21 Days in Combination With Paclitaxel/Carboplatin Chemotherapy in Subjects With Unresectable Stage III or Stage IV Melanoma.

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Time from randomization to documented tumor progression or death (median time of 124 days) ] [ Designated as safety issue: No ]
    PFS was calculated as the time (days) from date of randomization to date of first observed DP (per modified Response Evaluation Criteria In Solid Tumors [RECIST] or clinical judgment, whichever was earlier: CR, PR, stable disease, progressive disease) or death due to any cause, if death occurred before progression was documented. The actual date of tumor assessments was used for this calculation. PFS for subjects without progression or death was censored at the last date of tumor evaluation. PFS for subjects who had no tumor assessments after baseline and did not die was censored at 1 day.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Time from randomization to death (median time of 294 days) ] [ Designated as safety issue: No ]
    Overall survival (OS) was calculated as the number of days from date of randomization to death date. Subjects who had not died at the time of analysis were censored at their last contact date.

  • Time to Progression (TTP) [ Time Frame: Time from randomization to documented tumor progression (median time of 126 days) ] [ Designated as safety issue: No ]
    TTP was calculated as the time (days) from date of randomization to date of first observed disease progression (DP) (per modified RECIST or clinical judgment, whichever was earlier: CR, PR, stable disease, progressive disease). The actual dates of tumor assessments were used for this calculation. TTP for subjects without disease progression at the time of analysis, including subjects with death prior to progression, was censored at the last date of tumor evaluation. TTP for subjects who had no tumor assessments after baseline was censored at 1 day.

  • Duration of Response (DOR) [ Time Frame: Time from initial response to documented tumor progression or death (median time of 197 days) ] [ Designated as safety issue: No ]
    Duration of response was defined as the time from the first documented objective response of Partial Response (PR: At least a 30% decrease in the sum of the longest diameter [SLD] of target lesions, taking as reference the baseline SLD or better) or Complete Response (CR: Disappearance of all target lesions), whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). Duration of response for subjects who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment.

  • Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to the Visit When the Best Tumor Response Was Noted [ Time Frame: baseline and at visit when best response was noted (maximum treatment duration of 68.3 weeks) ] [ Designated as safety issue: No ]
    Change in ECOG PS is defined as an improvement (increase) or worsening (decrease) of at least one grade from the baseline ECOG score (from 0 [fully active] to 5 [dead]). Change in ECOG PS was recorded at the visit at which best confirmed response (BCR) using the modified RECIST (PR, CR, stable disease or Progressive Disease (PD)) was first noted (the change was 7% for both Sorafenib and Placebo). The BCR is the BCR recorded from the start of the treatment until DP/recurrence (taking as reference for DP, the smallest measurements recorded since treatment started).


Enrollment: 270
Study Start Date: May 2005
Study Completion Date: January 2009
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib (Nexavar, BAY43-9006)
Sorafenib, 400 mg orally, 2 tablets (200 mg each) bid (bis in die [twice daily]) on Study Days 2 to 19 + Paclitaxel (225 mg/m^2 iv [Intravenous]) and Carboplatin (AUC [area under the curve] 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.
Drug: Sorafenib (Nexavar, BAY43-9006)
Sorafenib, 400 mg po (per os), 2 tablets (200 mg each) bid Study Days 2-19
Drug: Carboplatin/Paclitaxel
Paclitaxel (225 mg/m^2 iv) and Carboplatin (AUC 6 iv) on Study Day 1
Active Comparator: Carboplatin/Paclitaxel (C/P)
Placebo, 2 tablets bid on Study Days 2-19 + Paclitaxel (225 mg/m^2 iv) and Carboplatin (AUC 6 iv) on Study Day 1 (21 days per cycle) for double-blind (DB) treatment. Subjects who discontinued DB treatment with complete response (CR), partial response (PR) or stable disease (SD) entered active follow up period. Subjects who discontinued DB treatment with disease progression (DP) entered long term follow up period.
Drug: Carboplatin/Paclitaxel
Paclitaxel (225 mg/m^2 iv) and Carboplatin (AUC 6 iv) on Study Day 1
Drug: Placebo
Placebo, 2 tablets bid Study Days 2-19

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who have a life expectancy of at least 12 weeks
  • Subjects with histologically or cytologically confirmed unresectable (Stage III) or metastatic (Stage IV) melanoma
  • Subjects must have progressed after receiving at least one cycle of DTIC or TMZ containing regimen
  • Subjects who have an ECOG PS of 0 or 1
  • Measurable disease defined as at least one lesion that can be accurately and serially measured per the modified RECIST criteria

Exclusion Criteria:

  • Primary ocular or mucosal melanoma
  • Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta [Noninvasive papillary carcinoma], Tis [Carcinoma in situ: "flat tumor"]& T1 [Tumor invades subepithelial connective tissue]) or any cancer curatively treated < 5 years prior to study entry
  • History of cardiac disease
  • Known history of human immunodeficiency virus (HIV) infection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00111007

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States, 35243
United States, Arizona
Tucson, Arizona, United States, 85724
United States, California
Los Angeles, California, United States, 90025
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Tampa, Florida, United States, 33612
United States, Illinois
Chicago, Illinois, United States, 60612
Park Ridge, Illinois, United States, 60068
United States, Kentucky
Louisville, Kentucky, United States, 40202
United States, Missouri
St. Louis, Missouri, United States, 63110
United States, Nebraska
Omaha, Nebraska, United States, 68114
United States, New Jersey
Montclair, New Jersey, United States, 07042
United States, New York
Buffalo, New York, United States, 14263
New York, New York, United States, 10065
United States, Ohio
Columbus, Ohio, United States, 43221
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Nashville, Tennessee, United States, 37232-6307
United States, Texas
Houston, Texas, United States, 77030
United States, Virginia
Charlottesville, Virginia, United States, 22908
United States, Washington
Seattle, Washington, United States, 98109-1023
Australia, New South Wales
Camperdown, New South Wales, Australia, 2050
Warartah, New South Wales, Australia, 2300
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Brisbane, Queensland, Australia, 4101
Australia, Victoria
East Melbourne, Victoria, Australia, 3002
Heidelberg, Victoria, Australia, 3084
Malvern, Victoria, Australia, 3144
Melbourne, Victoria, Australia, 3004
Australia, Western Australia
Nedlands, Western Australia, Australia, 6009
Canada, Alberta
Calgary, Alberta, Canada, T2N 4N2
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
London, Ontario, Canada, N6A 4L6
Toronto, Ontario, Canada, M4N 3M5
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Montreal, Quebec, Canada, H3T 1E2
France
Bordeaux, France, 33000
Boulogne-billancourt, France, 92104
Brest, France, 29285
Lyon Cedex, France, 39373
Montpellier Cedex, France, 34298
Paris, France, 75010
Paris, France, 75634
Villejuif, France, 94805
Germany
Heidelberg, Baden-Württemberg, Germany, 69112
Mannheim, Baden-Württemberg, Germany, 68135
Tübingen, Baden-Württemberg, Germany, 72076
München, Bayern, Germany, 81675
Frankfurt, Hessen, Germany, 60590
Frankfurt, Hessen, Germany, 60488
Essen, Nordrhein-Westfalen, Germany, 45122
Trier, Rheinland-Pfalz, Germany, 54290
Homburg, Saarland, Germany, 66421
Kiel, Schleswig-Holstein, Germany, 24105
Berlin, Germany, 12200
Netherlands
Amsterdam, Netherlands, 1066 CX
Rotterdam, Netherlands, 3075 EA
Utrecht, Netherlands, 3584 CX
United Kingdom
Southampton, Hampshire, United Kingdom, SO16 6YD
Leicester, Leicestershire, United Kingdom, LE1 5WW
Bebington, Merseyside, United Kingdom, CH63 4JY
Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
Sutton, Surrey, United Kingdom, SM2 5PT
Leeds, West Yorkshire, United Kingdom, LS9 7TF
London, United Kingdom, SW3 6JJ
London, United Kingdom, SE1 9RT
Manchester, United Kingdom, M20 4BX
Swansea, United Kingdom, SA2 8QA
Sponsors and Collaborators
Bayer
Onyx Pharmaceuticals
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00111007     History of Changes
Obsolete Identifiers: NCT00262912
Other Study ID Numbers: 11718, 2005-000941-12
Study First Received: May 16, 2005
Results First Received: January 27, 2011
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Sorafenib
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014