Lenalidomide, Docetaxel, and Carboplatin in Treating Patients With Advanced Solid Tumors

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of lenalidomide when administered with docetaxel and carboplatin in patients with advanced solid tumors.

Secondary

• Determine the safety and toxic effects of this regimen in these patients.
• Determine, preliminarily, the clinical activity of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of lenalidomide.

Patients receive docetaxel IV over 1 hour followed by carboplatin IV on day 1. Patients also receive oral lenalidomide once daily on days 1-14. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease after completion of 6 courses of treatment may continue lenalidomide alone once daily on days 1-14. Patients whose disease is stable or responding after completing 2 or 4 courses and who are unable to tolerate further chemotherapy may continue lenalidomide alone once daily on days 1-14, at the investigator's discretion. Treatment with lenalidomide repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of lenalidomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6-8 patients are treated at the MTD.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven solid tumor
• Measurable or evaluable disease
• Refractory to standard treatment
• No prior failure of a docetaxel and carboplatin regimen except in the adjuvant setting
• History of brain disease allowed, provided the following criteria are met:

• Brain disease previously treated with radiotherapy or surgery
• Asymptomatic with no active brain disease, as documented by CT scan or MRI, for at least 3 months

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine ≤ 1.5 mg/dL
• Bilirubin normal
• AST and ALT ≤ 2 times upper limit of normal (ULN) (5 times ULN if hepatic metastases are present)
• Alkaline phosphatase ≤ 3 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after completion of study treatment
• No serious medical condition, laboratory abnormality, or psychiatric illness that would preclude giving informed consent, expose the patient to unacceptable risk, or affect the interpretation of study data
• No known hypersensitivity to thalidomide
• No history of erythema nodosum, characterized by a desquamating rash, while taking thalidomide or similar drugs
• No pre-existing peripheral neuropathy ≥ grade 2
• No known hypersensitivity or intolerance to taxanes
• No known HIV positivity
• No known infectious hepatitis, types A, B, or C

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No more than 2 prior chemotherapy regimens
• At least 28 days since prior cancer therapy, including radiotherapy, biologic therapy, hormonal therapy, chemotherapy, or surgery
• At least 28 days since any other prior investigational drug or therapy
• No prior lenalidomide
• No other concurrent chemotherapy or biologic therapy
• No concurrent radiotherapy
• No concurrent use of any other anticancer agents or treatments
• No prophylactic granulocyte colony-stimulating factors (G-CSF) during the first course of study treatment
• No concurrent prophylactic antibiotics
• No concurrent treatment with the following medications:

• Systemic corticosteroids (except as prophylaxis for docetaxel administration)
• Estrogens
• Azoles
• Macrolides
• Cyclosporine
• Rifampin
• Phenytoin