Treatment for Subjects With Unresectable Stage III or Stage IV Melanoma

Back to results

Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Sorafenib (Nexavar, BAY43-9006)

Placebo

Dacarbazine

About this trial

This is an interventional treatment trial for Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Sorafenib (Nexavar, BAY43-9006) + Dacarbazine

Placebo + Dacarbazine

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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 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.

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.

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).

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.

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.

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.

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.

Full Information

NCT ID

NCT00110994

First Posted

May 16, 2005

Last Updated

May 13, 2015

Sponsor

Bayer

Collaborators

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT00110994

Brief Title

Treatment for Subjects With Unresectable Stage III or Stage IV Melanoma

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2015

Overall Recruitment Status

Completed

Study Start Date

April 2005 (undefined)

Primary Completion Date

October 2006 (Actual)

Study Completion Date

March 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

Collaborators

Amgen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cancer, Melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

101 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sorafenib (Nexavar, BAY43-9006) + Dacarbazine

Arm Type

Experimental

Arm Description

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.

Arm Title

Placebo + Dacarbazine

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Sorafenib (Nexavar, BAY43-9006)

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Dacarbazine

Intervention Description

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

Primary Outcome Measure Information:

Title

Progression Free Survival (PFS)

Description

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)

Secondary Outcome Measure Information:

Title

Overall Survival (OS)

Description

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)

Title

Number of Participants in Tumor Response Categories

Description

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

Title

Time to Progression (TTP)

Description

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.

Time Frame

Time from randomization to documented tumor progression (median time of 148 days)

Title

Duration of Response (DOR)

Description

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)

Title

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

Description

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