Conditions: Melanoma (Skin)
Keywords: recurrent melanoma stage III melanoma stage IV melanoma
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 169
Healthy volunteers: no

Brief 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.

Arms:
arm 1: Patients who were temozolomide naive and had no brain metastases received 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 2: Patients who were temozolomide naive and had no brain metastases received sorafenib tosylate as in arm A and oral TMZ once daily on days 1-5 and 29-33. arm 3: Patient with or without treated brain metastases who were treated with prior temozolomide and progressed were treated with 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 4: Patients with treated brain metastases were treated with sorafenib tosylate as in arm B and oral TMZ once daily on days 1-5 and 29-33.

Interventions: intervention 1: sorafenib tosylate intervention 2: temozolomide
Intervention descriptions: intervention 1: Given orally intervention 2: Given orally

Protocol document: