Clinical trial NCT00349206 (phase 1, status: completed)
Conditions: melanoma, recurrent melanoma, stage iii melanoma, stage iv melanoma
ICD codes: C43.0, C43.31, D03.9, C43.51, C43.9, D03.0, C43.4, G47.13, J01.41, K11.22, K12.0, N96, F33.8, G03.2, C43.0, C43.31, D03.9, C43.51, C43.9, D03.0, C43.4, C43.0, C43.31, D03.9, C43.51, C43.9, D03.0, C43.4
Drugs: sorafenib tosylate, temsirolimus
SMILES: CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1, CN1N=NC2=C(N=CN2C1=O)C(N)=O
Eligibility criteria:

        Criteria:

          -  Histologically or cytologically confirmed melanoma, meeting 1 of the following
             criteria: recurrent or unresectable stage III disease, stage IV disease, non-choroidal
             origin.

          -  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 this
             study.

          -  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
             compliance.

          -  No traumatic injury within the past 3 weeks.

          -  No more than 1 prior systemic chemotherapy regimen for metastatic melanoma (Phase II).

          -  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
             weight heparin).

          -  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 PT INR < 1.1 times ULN.

          -  Unidimensionally measurable disease >= 20 mm by conventional techniques or >= 10 mm by
             spiral 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.

          -  WBC >= 3,000/mm³

          -  Absolute neutrophil count >= 1,500/mm³

          -  Platelet count >= 100,000/mm³

          -  Serum cholesterol =< 350 mg/dL

          -  Triglycerides =< 400 mg/dL

          -  AST/ALT =< 2.5 times upper limit of normal.

          -  No peripheral neuropathy > grade 2.

          -  At least 5 years since prior chemotherapy for other types of cancer.