A Phase II, Multi-Center, Open-Label, Uncontrolled Study to Evaluate the Efficacy and Safety of Sorafenib Given Daily in Combination With Repeated 21-Day Cycles of Dacarbazine (DTIC) Chemotherapy in Subjects With Advanced Metastatic Melanoma

• ClinicalTrials.gov Identifier: NCT00492297
• Recruitment Status: Completed
• First Posted: June 27, 2007
• Results First Posted: January 25, 2011
• Last Update Posted: October 31, 2014
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Study Description

Brief Summary:

The purpose of this study is to see whether a new type of anti-cancer drug, known as BAY 43-9006, can be given safely and with good effect in combination with dacarbazine (DTIC). DTIC is the current standard chemotherapy drug given for melanoma that has spread through the body. Although this drug can be effective on its own and is generally well tolerated, not all patients will benefit, so there is a need to test new drugs and drug combinations for treating melanoma.

Condition or disease	Intervention/treatment	Phase
Melanoma	Drug: Sorafenib (Nexavar, BAY43-9006) + Dacarbazine (DTIC)	Phase 2

Detailed Description:

Issues on "Safety" outcomes are addressed in the Adverse Event section.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 83 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Multi-center, Open-label, Uncontrolled Study to Evaluate the Efficacy and Safety of BAY 43-9006 Given Daily in Combination With Repeated 21-Day Cycles of Dacarbazine (DTIC) Chemotherapy in Subjects With Advanced Metastatic Melanoma.
• Study Start Date: April 2005
• Actual Primary Completion Date: June 2008
• Actual Study Completion Date: July 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Sorafenib + Dacarbazine; Dacarbazine 1000 mg/m^2 on day one of repeated 21 day cycles, in combination with daily continuous oral sorafenib (Nexavar, BAY 43-9006), 400 mg twice a day (bid)	Drug: Sorafenib (Nexavar, BAY43-9006) + Dacarbazine (DTIC); Dacarbazine 1000 mg/m^2 on day one of repeated 21 day cycles, in combination with daily continuous oral sorafenib (Nexavar, BAY 43-9006), 400 mg twice a day (bid)

Outcome Measures

Primary Outcome Measures :

1. Overall Best Response [ Time Frame: during or within 30 days after active therapy ]
   Best Overall Response (BOR): Best tumor response achieved during or within 30 days after active therapy confirmed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR): The disappearance of all target and non-target lesions. Partial response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD was defined as steady state of disease, PD was defined as an increase of at least 20% increase in the sum of the LD of target lesions or appearance of new lesions.

Secondary Outcome Measures :

1. Progression-free Survival [ Time Frame: from start of treatment until progression or death before progression (median 259 days) ]
   Progression-free Survival (PFS) was the time from the first dose of combination therapy to disease progression (radiological or clinical, whichever is earlier) or death (if death occurs before progression is documented). PFS for subjects without tumor progression or death at the time of analysis were censored at the date of last tumor evaluation.
2. Percentage of Subjects With Progression-free Survival at Specific Time-points [ Time Frame: from start of treatment until progression or death before progression after 3, 6 and 12 months ]
   Progression-free Survival (PFS) was the time from the first dose of combination therapy to disease progression (radiological or clinical, whichever is earlier) or death (if death occurs before progression is documented). PFS for subjects without tumor progression or death at the time of analysis were censored at the date of last tumor evaluation.
3. Overall Survival [ Time Frame: from start of treatment until death (median 259 days) ]
   Overall Survival was the number of days from the date that combination treatment started until the date of death.
4. Duration of Response [ Time Frame: from confirmed Complete Response (CR) or Partial Response (PR) until Progressive Disease (PD) (median 259 days) ]
   Duration of Response was assessed in subjects who showed a Partial Response (PR) or Complete Response (CR). It was defined as the time from the first documented objective response to Progressive Disease (PD), or death if before documented progression. Duration of response for subjects who have not progressed or died at the time of analysis was censored at the date of last tumor assessment.
5. Duration of Complete Response [ Time Frame: from confirmed CR until PD (median 259 days) ]
   Duration of complete response was the number of days from the date that a complete response was first documented to the date that recurrent or progressive disease was first objectively documented (if patient progressed then censored=no) or to last observation (if patient did not progress then censored=yes).
6. Duration of Partial Response [ Time Frame: from confirmed PR until PD (median 259 days) ]
   Duration of partial response was the number of days from the date that a partial response was first documented to the date that recurrent or progressive disease was first objectively documented (if patient progressed then censored=no) or to last observation (if patient did not progress then censored=yes).
7. Disease Control (DC) [ Time Frame: after start of treatment, at 6 months and 12 months ]
   DC was defined as the total number of subjects whose best response was not progressive disease (PD) (total number of CRs + total number of PRs + total number of Stable Diseases (SD)). The DC at specific time points could also be calculated as the total number of subjects whose response was not PD at that time point.
8. Duration of Stable Disease [ Time Frame: from start of therapy to PD, only in non-responders (median 259 days) ]
   Duration of Stable Disease (DSD), defined as the time from the first documented objective evidence of Stable Disease (SD) to disease progression (DP) or death if death occurred before DP, was assessed in subjects who showed SD as best response. DSD for subjects who had not progressed or died was censored at the date of last tumor assessment.
9. Time to Response [ Time Frame: start of therapy to confirmed CR or PR (median 259 days) ]
   Time to Response in subjects who achieved an objective response (PR or CR with confirmation) was measured from the date of starting study combination treatment until the earliest date that the response was first documented.
10. Time to Progression [ Time Frame: From start of treatment until progression (median 259 days) ]
    Time to Progression was the number of days from the start of therapy to progression (if patient progressed then censored=no) or to the last observation at which the patient was known to have not progressed, that is, the last observation with a best response of CR, PR, or SD.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subjects with advanced, metastatic, histologically confirmed melanoma, for whom treatment with dacarbazine is considered medically acceptable
• Age >= 18 years
• Subject has measurable and evaluable disease defined as at least one metastatic lesion that can be accurately and serially measured by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scan as per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Cutaneous lesions measuring at least 20mm in longest diameter can be considered measurable (and therefore target lesions) via color photography including a ruler
• Subject has biopsiable disease at baseline and is willing to provide biopsy samples, or does not have biopsiable disease at baseline
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

Exclusion Criteria:

• Primary ocular or mucosal melanoma (cutaneous vulval melanoma is permitted)
• 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, Tis & T1] or any cancer curatively treated > 3 years prior to study entry
• (Active coronary artery disease or ischemia (myocardial infarction more than 6 months prior to study entry is allowed)
• Uncontrolled hypertension (> grade 2 National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0)
• Active, clinically serious infections (> grade 2 NCI-CTCAE version 3.0)
• Subjects with seizure disorder requiring medication are excluded
• History of or suspected Human Immunodeficiency Virus (HIV) infection, or chronic hepatitis B or C
• Symptomatic metastatic brain or meningeal tumors unless the subject is > 6 months from definitive therapy, has a negative imaging study within 4 weeks prior to study entry and is clinically stable with respect to the tumor at the time of study entry. Also the subject must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies)
• Pregnant or breast-feeding subjects

Contacts and Locations

Locations

France

Bordeaux, France, 33000

Lyon Cedex, France, 39373

Toulouse, France, 31052

Villejuif, France, 94805

United Kingdom

Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ

Southampton, Hampshire, United Kingdom, SO16 6YD

Northwood, Middlesex, United Kingdom, HA6 2RN

Sutton, Surrey, United Kingdom, SM2 5PT

London, United Kingdom, NW3 2QG

London, United Kingdom, SE1 7EH

London, United Kingdom, SW3 6JJ

Manchester, United Kingdom, M20 4BX

Sponsors and Collaborators

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

Additional Information:

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Publications of Results:

Eisen T, Marais R, Affolter A, Lorigan P, Robert C, Corrie P, Ottensmeier C, Chevreau C, Chao D, Nathan PD, Jouary T, Harries M, Negrier S, Montegriffo E, Ahmad T, Gibbens I, James MG, Strauss UP, Prendergast S, Gore ME. Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies. Br J Cancer. 2011 Jul 26;105(3):353-9. doi: 10.1038/bjc.2011.257. Epub 2011 Jul 12.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00492297
• Other Study ID Numbers: 11538; 2004-000725-30 ( EudraCT Number )
• First Posted: June 27, 2007
• Results First Posted: January 25, 2011
• Last Update Posted: October 31, 2014
• Last Verified: October 2014

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; Sorafenib; Dacarbazine; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Alkylating; Alkylating Agents