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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
101
Sorafenib, 400 mg, 2 tablets (200 mg each) po (per os) bid (twice daily) Study days 1-21
Placebo, 2 tablets, po (per os) bid (twice daily) Study days 1-21
Dacarbazine, 1000 mg/m\^2 intravenous on Study Day 1
Unnamed facility
Tucson, Arizona, United States
Unnamed facility
Aurora, Colorado, United States
Unnamed facility
Lakeland, Florida, United States
Progression Free Survival (PFS)
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.
Time frame: Time from randomization to documented tumor progression or death (the maximum treatment duration of 71.1 weeks)
Overall Survival (OS)
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 frame: Time from randomization to death (the maximum treatment duration of 71.1 weeks)
Number of Participants in Tumor Response Categories
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 frame: Every 6 weeks from the start of the treatment until the end of treatment visit with a median of 134 days
Time to Progression (TTP)
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.
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Unnamed facility
Park Ridge, Illinois, United States
Unnamed facility
Boston, Massachusetts, United States
Unnamed facility
Boston, Massachusetts, United States
Unnamed facility
Boston, Massachusetts, United States
Unnamed facility
St Louis, Missouri, United States
Unnamed facility
Omaha, Nebraska, United States
Unnamed facility
Charlotte, North Carolina, United States
...and 4 more locations
Time frame: Time from randomization to documented tumor progression (median time of 148 days)
Duration of Response (DOR)
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.
Time frame: Time from initial response to documented tumor progression or death (median time of 188 days)
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to the Visit When the Best Tumor Response Was Noted
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).
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
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
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.
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
Change of European Quality of Life 5-dimensional (EQ-5D) Questionnaire Index Score From Baseline to the End of Treatment
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.
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
Change of European Quality of Life Visual Analogue Scale (EQ-VAS) Score From Baseline to the Visit at Which Best Response Was First Noted
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.
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
Change of European Quality of Life Visual Analogue Scale (EQ-VAS) Score From Baseline to the End of Treatment
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.
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