Temozolomide and Sorafenib in Treating Patients With Metastatic or Unresectable Melanoma
Condition: Melanoma (Skin)
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop
      the growth of tumor cells, either by killing the cells or by stopping them from dividing.
      Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth and by blocking blood flow to the tumor. Giving temozolomide together with sorafenib
      may kill more tumor cells.

      PURPOSE: This randomized phase II trial is studying two different schedules of temozolomide
      when given together with sorafenib to compare how well they work in treating patients with
      metastatic or unresectable melanoma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To measure the progression-free survival of patients with metastatic or unresectable
           melanoma with no brain metastasis or no prior treatment with temozolomide (TMZ) treated
           with sorafenib tosylate in combination with two different schedules (extended daily
           dosing vs standard dosing) of TMZ.

        -  To measure the progression-free survival of patients with or without brain metastasis
           and prior treatment with TMZ treated with sorafenib in combination with extended daily
           dosing of TMZ.

        -  To measure the progression-free survival of patients with brain metastasis and no prior
           treatment with TMZ treated with sorafenib in combination with standard dosing TMZ.

        -  To estimate the median time to progression in all patients.

        -  To quantify the number and percent of patients who have stable disease after 6 months of
           treatment (failure to progress).

        -  To choose the optimal combination dosing regimen for further study.

      Secondary

        -  To estimate and define the objective response rate in these patients.

        -  To characterize the duration of objective responses in these patients.

        -  To estimate the incidence of new symptomatic brain metastasis in these patients.

        -  To measure overall survival of these patients.

      OUTLINE: This is a multicenter study. Patients are stratified according to prior brain
      metastases (yes vs no) and prior treatment with temozolomide (TMZ) (yes vs no). Patients with
      no prior brain metastases who did not receive prior treatment with TMZ are randomized to 1 of
      2 treatment arms. These patients are further stratified according to prior treatment with
      sorafenib tosylate (yes vs no). Patients with or without prior brain metastases who received
      prior treatment with TMZ are assigned to arm I. Patients with prior brain metastases who did
      not receive prior treatment with TMZ are assigned to arm II.

        -  Arm I: Patients receive oral sorafenib tosylate twice daily on days -7 to 56 of course 1
           and on days 1-56 of all subsequent courses. Patients also receive oral TMZ once daily on
           days 1-42.

        -  Arm II: Patients receive sorafenib tosylate as in arm I and oral TMZ once daily on days
           1-5 and 29-33.

      In both arms, courses repeat every 8 weeks in the absence of disease progression or
      unacceptable toxicity.
    

Intervention name(s): sorafenib tosylate; temozolomide
Intervention type(s): Drug; Drug
Intervention description(s): Given orally; Given orally
Other intervention name(s): nexavar; temodar
Intervention MeSH terms: Temozolomide; Sorafenib
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 4 arm parallel phase II study Arms A and B are randomized to different schedules of temozolomide Arm C is prior temozolomide-refractory patients Arm D is brain metastases patients
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent melanoma; stage III melanoma; stage IV melanoma