Phase 2 Study of the Combination of BAY 43-9006 (Sorafenib) and CCI-779 (Temsirolimus) in Patients With Metastatic Melanoma
- Histologically or cytologically confirmed melanoma, meeting 1 of the following
criteria: recurrent or unresectable stage III disease, stage IV disease,
- Tumor must be accessible to biopsy unless appropriate tumor sample collection has
occurred within the past 3 months and patient agrees to provide these samples for
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Bilirubin normal
- Creatinine normal or creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 30 days after
completion of study treatment.
- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to sorafenib or temsirolimus.
- No uncontrolled hypertension, defined as systolic blood pressure > 140 mm Hg on 2
separate days < 1 week prior to study entry OR diastolic pressure > 90 mm Hg on 2
separate days < 1 week prior to study entry.
- No evidence of bleeding diathesis or coagulopathy.
- No condition that would impair the ability to swallow pills (e.g., gastrointestinal
tract disease resulting in an inability to take oral medication; requirement for IV
alimentation; or active peptic ulcer disease).
- No uncontrolled illness including, but not limited to, any of the following: ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia or psychiatric illness or social situations that would limit study
- No traumatic injury within the past 3 weeks.
- No more than 1 prior systemic chemotherapy regimen for metastatic melanoma (Phase
- No prior sorafenib, temsirolimus, or any other agents targeting raf, vascular
endothelial growth factor (VEGF)/VEGF receptor, or mTOR (Phase II).
- No prior surgical procedures affecting absorption.
- At least 3 weeks since prior major surgery.
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
for melanoma and recovered.
- At least 4 weeks since prior radiotherapy and recovered.
- Prior biologic or immunotherapeutic regimens allowed.
- Prior regional chemotherapy regimens (e.g., isolated limb perfusion) allowed but only
1 prior regional chemotherapy regimen allowed if all target lesions are within the
prior regional treatment field.
- No concurrent enzyme-inducing antiepileptic drugs including, but not limited to, any
of the following: phenytoin, carbamazepine, phenobarbital, rifampin or Hypericum
perforatum (St. John's wort).
- No concurrent prophylactic hematopoietic colony-stimulating factors.
- No other concurrent investigational agents.
- No other concurrent anticancer agents or therapies for this cancer.
- No concurrent full-dose anticoagulation (i.e., warfarin, IV heparin, or low-molecular
- No concurrent grapefruit or grapefruit juice.
- No concurrent combination antiretroviral therapy for HIV-positive patients.
- Concurrent prophylactic anticoagulation therapy (e.g., low-dose warfarin) allowed
provided prothrombin time (PT) international normalized ratio (INR) < 1.1 times upper
limits of normal (ULN).
- Unidimensionally measurable disease >= 20 mm by conventional techniques or >= 10 mm
by spiral computed tomography (CT) scan (longest diameter to be recorded) and margins
of visible cutaneous metastatic lesions should be clearly defined and measured in at
least one dimension as >= 10 mm.
- No known brain metastases unless the following criteria are met: no radiographical
evidence of recurrences in the brain >= 3 months after complete resection of the
brain metastases, asymptomatic brain metastases stable for >= 3 months since
whole-brain radiation therapy and/or stereotactic radiosurgery and must not require
steroid for brain metastases.
- White Blood Count (WBC) >= 3,000/mm³
- Absolute neutrophil count >= 1,500/mm³
- Platelet count >= 100,000/mm³
- Serum cholesterol =< 350 mg/dL
- Triglycerides =< 400 mg/dL
- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 2.5 times upper
limit of normal.
- No peripheral neuropathy > grade 2.
- At least 5 years since prior chemotherapy for other types of cancer.