Temozolomide and Sorafenib in Treating Patients With Metastatic or Unresectable Melanoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2009 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00602576
First received: January 25, 2008
Last updated: August 12, 2009
Last verified: August 2009

January 25, 2008
August 12, 2009
January 2005
March 2008   (final data collection date for primary outcome measure)
Progression-free survival [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00602576 on ClinicalTrials.gov Archive Site
  • Response rate [ Designated as safety issue: No ]
  • Development of new brain metastasis [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Temozolomide and Sorafenib in Treating Patients With Metastatic or Unresectable Melanoma
RANDOMIZED PHASE II STUDY COMPARING TWO SCHEDULES OF TEMOZOLOMIDE IN COMBINATION WITH BAY43-9006 IN PATIENTS WITH ADVANCED MELANOMA

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.

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.

Interventional
Phase 2
Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Melanoma (Skin)
  • Drug: sorafenib tosylate
    Given orally
  • Drug: temozolomide
    Given orally
  • Experimental: 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.
    Interventions:
    • Drug: sorafenib tosylate
    • Drug: temozolomide
  • Experimental: Arm II
    Patients receive sorafenib tosylate as in arm I and oral TMZ once daily on days 1-5 and 29-33.
    Interventions:
    • Drug: sorafenib tosylate
    • Drug: temozolomide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
167
Not Provided
March 2008   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed melanoma

    • Metastatic or unresectable disease
  • Measurable disease by RECIST criteria

    • Cutaneous lesions measuring at least 1 cm will be considered measurable disease
  • Brain metastases allowed provided patient completed radiotherapy, if radiotherapy was clinically indicated at the time of diagnosis, AND discontinued steroids prior to study enrollment

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • WBC ≥ 3,000/mm³
  • Absolute granulocyte count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Serum creatinine ≤ 2.0 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 times ULN (< 3.0 times ULN if Gilbert's disease is present)
  • AST or ALT ≤ 2.5 times ULN (≤ 5.0 times ULN if liver metastases are present)
  • INR ≤ 1.5 (if on anticoagulation, baseline INR must be < 1.5 before starting anticoagulation)
  • PTT normal
  • No other concurrent malignancies, except basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or ductal or lobular carcinoma in situ of the breast
  • No concurrent serious illness including, but not limited to, any of the following:

    • Ongoing or active infection requiring parenteral antibiotics
    • Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, myocardial infarction, unstable angina)
    • New York Heart Association class II-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Peripheral vascular disease ≥ grade II within the past year
    • Psychiatric illness/social situation that would limit compliance with study requirements
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No HIV positivity

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from all prior therapy
  • Prior radiotherapy allowed

    • If radiotherapy has been administered to a lesion, there must be radiographic evidence of progression of that lesion for that lesion to constitute measurable disease or to be included in the measured target lesions
  • Prior temozolomide or sorafenib tosylate allowed
  • At least 4 weeks since prior chemotherapy
  • At least 4 weeks since prior active immunotherapy (aldesleukin, interferon, sargramostim [GM-CSF], or CTLA-4)
  • At least 4 weeks since prior and no other concurrent investigational anticancer therapy (except vaccines)
  • No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00602576
CDR0000580808, UPCC-06604, UPCC-802514, SPRI-UPCC-06604
Not Provided
Amy Kramer, Abramson Cancer Center of the University of Pennsylvania
University of Pennsylvania
National Cancer Institute (NCI)
Investigator: Amy Kramer, RN, MPA Abramson Cancer Center of the University of Pennsylvania
National Cancer Institute (NCI)
August 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP