Treatment for Subjects 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:
NCT00110994
First received: May 16, 2005
Last updated: May 26, 2014
Last verified: May 2014
  Purpose

This is a randomized, double blind, placebo controlled, multicenter, phase II study to compare the anti-tumor activity as measured by progression-free survival (PFS) and the tolerability of Sorafenib in combination with Dacarbazine (DTIC) versus DTIC in combination with placebo in subjects with unresectable Stage III or Stage IV melanoma who have not received prior cytotoxic chemotherapy. A total of approximately 98 subjects will be randomized to receive DTIC + Sorafenib or DTIC + Placebo.


Condition Intervention Phase
Cancer
Melanoma
Drug: Sorafenib (Nexavar, BAY43-9006)
Drug: Placebo
Drug: Dacarbazine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Phase II Randomized, Placebo Controlled Study of Sorafenib in Repeated Cycles of 21 Days in Combination With Dacarbazine (DTIC) 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 (the maximum treatment duration of 71.1 weeks) ] [ 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 (the maximum treatment duration of 71.1 weeks) ] [ 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.

  • Number of Participants in Tumor Response Categories [ Time Frame: Every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days ] [ Designated as safety issue: No ]
    Tumor response was defined as the best response (confirmed complete response [CR], partial response [PR], stable disease [SD], or progressive disease [PD]) assessed using the Response Evaluation Criteria in Solid Tumors (RECIST). PR: At least a 30% decrease in the sum of the longest diameter [SLD] of target lesions, taking as reference the baseline SLD. CR: Disappearance of all target lesions. SD: Does not qualify for CR or PR. PD: at least a 20% increase in SLD taking as reference the smallest SLD recorded since treatment started or the appearance of one or more new lesions.

  • Time to Progression (TTP) [ Time Frame: Time from randomization to documented tumor progression (median time of 148 days) ] [ Designated as safety issue: No ]
    TTP was calculated as the time (days) from date of randomization to date of first observed disease progression (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 188 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 in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to the Visit When the Best Tumor Response Was Noted [ Time Frame: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days ] [ 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).

  • Change of European Quality of Life 5-dimensional (EQ-5D) Questionnaire Index Score From Baseline to the Visit at Which Best Response Was First Noted [ Time Frame: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days ] [ Designated as safety issue: No ]
    European Quality of Life 5-dimensional (EQ-5D) is a self-administered questionnaire developed to measure health status across 5 dimensions: Mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Each dimension has 3 levels of response: No problem (1), some problems (2), and extreme problems (3). The five dimensions are summarized into a single score, the EQ‑5D index score, which ranges between 0 and 1, with 0 representing the worst imaginable health state or death and 1 representing perfect health.

  • Change of European Quality of Life 5-dimensional (EQ-5D) Questionnaire Index Score From Baseline to the End of Treatment [ Time Frame: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days ] [ Designated as safety issue: No ]
    European Quality of Life 5-dimensional (EQ-5D) is a self-administered questionnaire developed to measure health status across 5 dimensions: Mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Each dimension has 3 levels of response: No problem (1), some problems (2), and extreme problems (3). The five dimensions are summarized into a single score, the EQ‑5D index score, which ranges between 0 and 1, with 0 representing the worst imaginable health state or death and 1 representing perfect health.

  • Change of European Quality of Life Visual Analogue Scale (EQ-VAS) Score From Baseline to the Visit at Which Best Response Was First Noted [ Time Frame: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days ] [ Designated as safety issue: No ]
    European Quality of Life Visual Analogue Scale (EQ-VAS) is a self-administered test that records the respondents' self-rated health status on a visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). Responders specify their scales by indicating a position along a continuous line between 0 and 100.

  • Change of European Quality of Life Visual Analogue Scale (EQ-VAS) Score From Baseline to the End of Treatment [ Time Frame: Baseline and every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days ] [ Designated as safety issue: No ]
    European Quality of Life Visual Analogue Scale (EQ-VAS) is a self-administered test that records the respondents' self-rated health status on a visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). Responders specify their scales by indicating a position along a continuous line between 0 and 100.


Enrollment: 101
Study Start Date: April 2005
Study Completion Date: March 2008
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib (Nexavar, BAY43-9006) + Dacarbazine
Sorafenib, 2 tablets (200 mg each) orally twice daily (bid) on study days 1-21 + Dacarbazine, 1000 mg/m^2 intravenous 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, 2 tablets (200 mg each) po (per os) bid (twice daily) Study days 1-21
Drug: Dacarbazine
Dacarbazine, 1000 mg/m^2 intravenous on Study Day 1
Active Comparator: Placebo + Dacarbazine
Placebo, 2 tablets orally twice daily on study days 1-21 + Dacarbazine, 1000 mg/m^2 intravenous 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: Placebo
Placebo, 2 tablets, po (per os) bid (twice daily) Study days 1-21
Drug: Dacarbazine
Dacarbazine, 1000 mg/m^2 intravenous on Study Day 1

  Eligibility

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

Inclusion Criteria:

  • Patients who have a life expectancy of at least 12 weeks
  • Patients with histologically or cytologically confirmed unresectable (Stage III) or metastatic (Stage IV) melanoma
  • Patients 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 < 3 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: NCT00110994

Locations
United States, Arizona
Tucson, Arizona, United States, 85724
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Lakeland, Florida, United States, 33805
United States, Illinois
Park Ridge, Illinois, United States, 60068
United States, Massachusetts
Boston, Massachusetts, United States, 02215
Boston, Massachusetts, United States, 02115-6084
Boston, Massachusetts, United States, 02114
United States, Missouri
St. Louis, Missouri, United States, 63110-1093
United States, Nebraska
Omaha, Nebraska, United States, 68114
United States, North Carolina
Charlotte, North Carolina, United States, 28203
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States, 15232
United States, South Carolina
Hilton Head Island, South Carolina, United States, 29926-2739
United States, Tennessee
Nashville, Tennessee, United States, 37232-6307
United States, Texas
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Bayer
Onyx Pharmaceuticals
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00110994     History of Changes
Other Study ID Numbers: 11715
Study First Received: May 16, 2005
Results First Received: January 26, 2011
Last Updated: May 26, 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
Dacarbazine
Sorafenib
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014