Temozolomide and Sorafenib in Treating Patients With Metastatic or Unresectable Melanoma
Condition: Melanoma (Skin)
MeSH terms: Melanoma
Intervention: sorafenib tosylate; temozolomide
Intervention description: Given orally; Given orally
Intervention MeSH terms: Temozolomide; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
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)
Enrollment: 169.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: recurrent melanoma; stage III melanoma; stage IV melanoma

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.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          1. Histologically or cytologically confirmed melanoma that is metastatic or unresectable.

          2. The following groups are eligible with regard to prior therapy in either the adjuvant
             or metastatic disease setting:

             a) No prior therapy c) Immunotherapy consisting of Interferon, Interleukin-2 or
             GM-CSF. d) Chemotherapy, either single-agent or combination. Prior temozolomide is
             allowable e) Vaccine therapy f) Prior sorafenib is allowable

             NB: There is no limit on the number of prior therapies

          3. Prior radiation therapy is allowed. However, if radiation has been administered to a
             lesion, there must be radiographic evidence of progression of that lesion in order for
             that lesion to constitute measurable disease or to be included in the measured target
             lesions.

          4. Measurable disease by RECIST criteria. Cutaneous lesions measuring at least 1 cm will
             be considered. Baseline CT or MRI scans of disease sites must be performed within 4
             weeks of study entry. For patients with bone metastases, a baseline bone scan must be
             performed within 4 weeks of study entry.

          5. Age > 18 years.

          6. Eastern Cooperative Oncology Group performance status of 0 or 1.

          7. Baseline laboratory values (evaluated within 14 days of randomization):

             White Blood Count > 3,000/mm3 Absolute Granulocyte Count > 1,500/mm3 Platelet Count >
             100,000/mm3 Serum creatinine < 2.0 x upper limit of normal (ULN) or serum creatinine
             clearance estimated by the MDRD formula Total Bilirubin < 1.5 x ULN (< 3.0 x ULN in
             the presence of Gilbert's disease AST/ALT < 2.5 x ULN (< 5.0 ULN in the presence of
             liver metastases) INR < 1.5 and a PTT within the upper limit of normal (if on
             anticoagulation baseline INR before starting anticoagulation must be <1.5)

          8. Patients must have discontinued active immunotherapy (IL-2, interferon, CTLA-4, etc.)
             or chemotherapy at least 4 weeks prior to entering the study and recovered from
             adverse events due to those agents. Patients must not receive any other
             investigational anticancer therapy during the period on study or the four weeks prior
             to entry, with the exception of vaccines.

          9. Patients with brain metastases must have completed radiation therapy if radiation is
             clinically indicated at the time of diagnosis and discontinued steroids prior to
             enrollment.

         10. The effects of sorafenib, temozolomide on the developing human fetus are unknown. For
             this reason and because antiangiogenic agents as well as other therapeutic agents used
             in this trial are known to be teratogenic, women of child-bearing potential and men
             must agree to use adequate contraception (hormonal or barrier method of birth control;
             abstinence) prior to study entry and for the duration of study participation. Should a
             woman become pregnant while participating in this study, she should inform her
             treating physician immediately. If a man impregnates a woman while participatig in
             this study, he should inform his treating physician immediately as well.

        EXCLUSION CRITERIA

          1. Patients must not have other current malignancies, other than basal cell skin cancer,
             squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in
             situ of the breast.

          2. Patients must not have a serious intercurrent illness including, but not limited to,
             ongoing or active infection requiring parental antibiotics, clinically significant
             cardiovascular disease (e.g. uncontrolled hypertension, myocardial infarction,
             unstable angina), New York heart association grade II or greater congestive heart
             failure, serious cardiac arrhythmia requiring medication, or grade II or greater
             peripheral vascular disease within 1 year prior to study entry, or psychiatric
             illness/social situations that would limit compliance with study requirements.

          3. Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs
             (phenytoin, carbamazepine or phenobarbital), rifampin or St. John's wort.

          4. Women must not be pregnant or breast-feeding as the agents used in this study may be
             teratogenic to a fetus and there is no information on the excretion of the agents or
             their metabolites into breast milk. All females of childbearing potential must have a
             blood test or urine study within 2 weeks prior to registration to rule out pregnancy.

          5. Because patients with immune deficiency are at increased risk of lethal infections
             when treated with bone marrow-suppressive therapy, HIV-positive patients are excluded
             from the study. For patients receiving combination anti-retroviral therapy, the
             potential impact of pharmacokinetic interactions with sorafenib, temozolomide is
             unknown. Appropriate studies may be undertaken in patients with HIV and those
             receiving combination anti-retroviral therapy in the future.