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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: October 23, 2014
Last verified: October 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

  Show 66 Study Locations
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: October 23, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on November 20, 2014