Pilot Trial of "Chemo-Switch" Regimen to Treat Advanced Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Concurrent decrescendo biochemotherapy regimen; Low-dose Temozolomide plus Sorafenib
Intervention description: Temozolomide: 200mg/m^2, daily, PO, days 1-4
Vinblastine: 1.5mg/m^2, daily, IV, days 1-4
Cisplatin: 20mg/m^2, daily IV, days 1-4
IL (interleukin)-2: - 18 milli-International unit (MIU)/m^2, IVCI (intravenous continual infusion), day 1
9 MIU/m^2, IVCI, day 2
4.5 MIU/m^2, IVCI, days 3 & 4
Interferon (IFN) alpha: 5 MIU/m^2, daily, SC (subcutaneously), days 1-5
5-day inpatient regimen, to be repeated every 21 days; Temozolomide: 75mg/m^2, PO, QD (quaque die), 6 weeks on/2 weeks off Sorafenib: 400mg, PO, BID, 8 weeks
Intervention MeSH terms: Temozolomide; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This research study is testing the "chemo-switch" strategy in melanoma, using biochemotherapy
      initially to shrink tumors and then switching to daily low-dose chemotherapy (temozolomide)
      together with sorafenib. The purpose of this study is to find out what effects (good and bad)
      biochemotherapy followed by temozolomide plus sorafenib have on melanoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must have histologically or cytologically confirmed melanoma that is locally advanced
             or metastatic. Cutaneous, mucosal, ocular, and unknown primary melanoma are all
             eligible.

          -  Must have measurable disease, defined by RECIST as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as
             >20mm with conventional techniques or >10mm with spiral CT scan.

          -  May have received prior radiation therapy to one or more non-index lesions (prior
             radiation to an index lesion is allowable only if progression of the irradiated lesion
             is demonstrated, with progression defined as an increase of 20% or more in the largest
             diameter) and/or one prior vaccine therapy for metastatic disease. Prior adjuvant
             therapy with IFN alpha-2b, vaccine, and/or granulocyte-macrophage colony-stimulating
             factor (GM-CSF) is permitted. At least 4 weks must have elapsed since the completion
             of any prior therapy.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Patients must have normal organ and marrow function as defined below:

          -  leukocytes >3,000/uL (microliters)

          -  absolute neutrophil count >1,500/uL

          -  platelets >100,000/uL

          -  total bilirubin <2.0mg/dL

          -  AST (Aspartate transaminase)(SGOT)/ALT (Alanine transaminase)(SGPT) <2.5 X
             institutional upper limit of normal

          -  creatinine <1.8mg/dL

          -  If >50 years of age with one or more cardiac risk factors, must demonstrate normal
             exercise stress test, stress thallium test, or comparable cardiac ischemia evaluation.

          -  Must be at least 2 weeks out from major surgery and be free of any active infection
             requiring antibiotics.

          -  Women of child-bearing potential and men must agree to use adequate contraception
             prior to study entry and for the duration of study participation. Women must
             demonstrate a negative pregnancy test prior to initiation of protocol therapy.

          -  Ability to understand and the willingness to sign a written informed consent form.

        Exclusion Criteria:

          -  Prior chemotherapy, cytokine therapy (including IL-2 or IFN alpha), or antibody
             therapy for metastatic disease. Prior vaccine therapy is permitted.

          -  May not be currently receiving any other antineoplastic treatments, including
             chemotherapy, biologic response modifiers, radiation, vaccine, or investigational
             agents.

          -  History of brain metastases.

          -  Autoimmune disorders that could result in life-threatening complications in the
             setting of IFN alpha and IL-2 treatment.

          -  History of sensitivity to E. coli-derived products.

          -  Concurrent use of corticosteroids or any medical condition likely to require the use
             of systemic corticosteroids.

          -  A seizure disorder currently requiring anti-epileptic medication.

          -  Uncontrolled intercurrent illness including, but not limited to, hypertension, active
             infection requiring antibiotic therapy, symptomatic congestive heart failure, unstable
             angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that
             would limit compliance with study requirements.

          -  Evidence of bleeding diathesis.

          -  Currently on therapeutic anticoagulation. Prophylactic anticoagulation (such as
             low-dose warfarin) of venous or arterial access devices is allowed provided the PT,
             PTT (Partial Thromboplastin Time), and international normalized ratio (INR) are
             normal.