Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Dacarbazine

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

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.

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.

Sorafenib, 400 mg, 2 tablets (200 mg each) po (per os) bid (twice daily) Study days 1-21

Sorafenib (Nexavar, BAY43-9006)

Placebo, 2 tablets, po (per os) bid (twice daily) Study days 1-21

Placebo

Dacarbazine, 1000 mg/m\^2 intravenous on Study Day 1

Bayer Study Director

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.

Treatment for Subjects With Unresectable Stage III or Stage IV Melanoma

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

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.

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.

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.

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 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 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).

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.

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.

Amgen

Bayer

Abbreviations used in the Adverse Events section: Absolute Neutrophil Count (ANC), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Central Nervous System (CNS), Common Terminology Criteria for Adverse Events (CTCAE), Gastro-Intestinal (GI), National Cancer Institute (NCI), Not Otherwise Specified (NOS)

Sorafenib (Nexavar, BAY43-9006) + Dacarbazine

Placebo + Dacarbazine

Total

Age, Continuous

<65 years

>=65 and <75 years

>=75 years

Age, Customized

Sex: Female, Male

Stage III

Stage IV M1a

Stage IV M1b

Stage IV M1c

Stage III: Clinical or radiological evidence of regional metastases (M), in either the lymph nodes or intra-lymphatic. Stage IV: M at any distant site. M1a: M to the skin, subcutaneous tissue, or lymph nodes. M1b: M to the lung. M1c: M to all other visceral sites or at any site associated with an elevated serum lactate dehydrogenase.

American Joint Committee on Cancer (AJCC) Stage at Study Entry

Status 0

Status 1

Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects a patient. The scale ranges from 0 (fully active) to 5 (dead). Subjects entering this study must have had an ECOG score of 0 or 1 (restricted in physically strenuous activity but ambulatory).

Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status

Normal

High

Missing

Lactate dehydrogenase (LDH) was assessed at study entry as part of a battery of tests to assess liver function. A typical normal range is 105 to 333 Units/Liter (U/L), but may vary across laboratories.

Lactate dehydrogenase (LDH) at study entry

Therapeutic Area Head

PFS was analyzed for the intent to treat (ITT) population, defined as all subjects randomized to treatment.

Progression Free Survival (PFS)

OS was analyzed for the intent to treat (ITT) population, defined as all subjects randomized to treatment.

Overall Survival (OS)

Not Evaluated

Tumor response was analyzed for the intent to treat (ITT) population, defined as all subjects randomized to treatment.

Number of Participants in Tumor Response Categories

TTP was analyzed for the intent to treat (ITT) population, defined as all subjects randomized to treatment.

Time to Progression (TTP)

DOR was analyzed for the intent to treat (ITT) population, defined as all subjects randomized to treatment.

Duration of Response (DOR)

missing

better

no change

worse

Change in ECOG performance status was analyzed for the intent to treat (ITT) population, defined as all subjects randomized to treatment.

Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to the Visit When the Best Tumor Response Was Noted

Change of EQ-5D questionnaire index score was analyzed for the intent to treat (ITT) population, defined as all subjects randomized to treatment.

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

Change of European Quality of Life 5-dimensional (EQ-5D) Questionnaire Index Score From Baseline to the End of Treatment

Change of EQ-VAS score was analyzed for the intent to treat (ITT) population, defined as all subjects randomized to treatment.

Spots Global Cancer Trial Database for Treatment for Subjects With Unresectable Stage III or Stage IV Melanoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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