Temozolomide and Everolimus in Treating Patients With Stage IV Melanoma That Cannot be Removed by Surgery
Condition: Melanoma (Skin)
MeSH terms: Melanoma
Intervention: everolimus; temozolomide
Intervention MeSH terms: Everolimus; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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.
      Everolimus may stop the growth of tumor cells by blocking blood flow to the tumor and by
      blocking some of the enzymes needed for cell growth. Giving everolimus together with
      temozolomide may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving everolimus together with
      temozolomide works in treating patients with stage IV melanoma that cannot be removed by
      surgery
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed melanoma with manifestations of metastatic disease.

          -  Unresectable stage IV malignant melanoma with measurable disease

               -  Measurable disease defined as at least one lesion with the longest diameter
                  measured as ≥ 20 mm by CT scan or MRI scan OR ≥ 10 mm by spiral CT

          -  No previously untreated or unstable active brain metastases within the past 3 months

          -  No known standard therapy for this disease that is potentially curative or proven
             capable of extending life expectancy

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-2

          -  Life expectancy ≥ 12 weeks

          -  ANC ≥ 1,500/μL

          -  Platelet count ≥ 100,000/μL

          -  Hemoglobin ≥ 9.0 g/dL

          -  Alkaline phosphatase ≤ 3 times institutional upper limit of normal (ULN)

          -  Creatinine ≤ 1.5 times ULN

          -  AST ≤ 3 times ULN

          -  INR ≤ 1.5

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients and their partners must use effective contraception during and for ≥
             8 weeks after completion of study treatment

          -  Able to return to a NCCTG institution for follow-up

          -  Able to forego foods high in fat content 2 hours prior to and 2 hours after
             administration of everolimus therapy

          -  Able to provide blood samples for research purposes

          -  No hypersensitivity to temozolomide, dacarbazine, or any analog of sirolimus

          -  No history of malignancy within the past 5 years except for basal cell or squamous
             cell carcinoma of the skin treated with local resection only

          -  No immunosuppression from any cause, including known HIV infection or chronic
             immunosuppressive therapy

          -  No impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of everolimus (e.g., ulcerative disease,
             uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome)

          -  No serious medical condition that may make it unsafe for a patient to enroll in study,
             including any of the following:

               -  Severely impaired lung function (FEV1 < 1 liter), unstable angina pectoris
                  (ongoing symptoms), ongoing symptomatic congestive heart failure (i.e., NYHA
                  class I-IV) refractory to appropriate therapy, or myocardial infarction within
                  the past 6 months, or serious uncontrolled cardiac arrhythmia

               -  Uncontrolled diabetes in spite of optimal therapy (i.e., a history of fasting
                  serum glucose > 150 mg/dL)

               -  Any active (acute or chronic) or uncontrolled infection/disorders

               -  Nonmalignant medical illnesses that are uncontrolled or whose control may be
                  jeopardized by the study treatment

               -  Liver disease (i.e., uncompensated cirrhosis or active hepatitis with elevated
                  liver enzymes)

          -  No bleeding diathesis

          -  No concurrent severe condition that would make it undesirable for the patient to
             participate in this trial or that would jeopardize compliance with the trial

        PRIOR CONCURRENT THERAPY:

          -  Must have recovered from effects of prior antineoplastic therapy

          -  At least 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)

          -  At least 4 weeks since prior immunotherapy

          -  At least 4 weeks since prior biologic therapy

          -  At least 4 weeks since prior radiosurgery

          -  At least 4 weeks since prior investigational therapy for melanoma

          -  No prior small bowel resection that may significantly alter the absorption of
             everolimus

          -  No prior sirolimus or its analogues

          -  No prior radiotherapy to > 30% of bone marrow

          -  No concurrent drugs that may induce CYP3A4 activity

          -  No concurrent warfarin

          -  No concurrent grapefruit or grapefruit juice

          -  No concurrent use or planned use of vaccines containing live virus