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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00492297
First received: June 26, 2007
Last updated: March 26, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Melanoma
Drug: Sorafenib (Nexavar, BAY43-9006) + Dacarbazine (DTIC)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Overall Best Response [ Time Frame: during or within 30 days after active therapy ] [ Designated as safety issue: No ]
    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:
  • Progression-free Survival [ Time Frame: from start of treatment until progression or death before progression (median 259 days) ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Overall Survival [ Time Frame: from start of treatment until death (median 259 days) ] [ Designated as safety issue: No ]
    Overall Survival was the number of days from the date that combination treatment started until the date of death.

  • Duration of Response [ Time Frame: from confirmed Complete Response (CR) or Partial Response (PR) until Progressive Disease (PD) (median 259 days) ] [ Designated as safety issue: No ]
    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.

  • Duration of Complete Response [ Time Frame: from confirmed CR until PD (median 259 days) ] [ Designated as safety issue: No ]
    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).

  • Duration of Partial Response [ Time Frame: from confirmed PR until PD (median 259 days) ] [ Designated as safety issue: No ]
    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).

  • Disease Control (DC) [ Time Frame: after start of treatment, at 6 months and 12 months ] [ Designated as safety issue: No ]
    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.

  • Duration of Stable Disease [ Time Frame: from start of therapy to PD, only in non-responders (median 259 days) ] [ Designated as safety issue: No ]
    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.

  • Time to Response [ Time Frame: start of therapy to confirmed CR or PR (median 259 days) ] [ Designated as safety issue: No ]
    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.

  • Time to Progression [ Time Frame: From start of treatment until progression (median 259 days) ] [ Designated as safety issue: No ]
    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.


Enrollment: 83
Study Start Date: April 2005
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00492297

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:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00492297     History of Changes
Other Study ID Numbers: 11538, 2004-000725-30
Study First Received: June 26, 2007
Results First Received: October 28, 2009
Last Updated: March 26, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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 April 23, 2014