Phase II Pilot Trial of "Chemo-Switch" Regimen of Biochemotherapy Followed by Daily Low-Dose Temozolomide Plus Sorafenib in Advanced Melanoma
- Must have histologically or cytologically confirmed melanoma that is locally advanced
or metastatic. Cutaneous, mucosal, ocular, and unknown primary melanoma are all
- 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
- Must be at least 2 weeks out from major surgery and be free of any active infection
- 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.
- 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
- 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