Docetaxel and Temozolomide in Treating Patients With Metastatic Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of docetaxel and temozolomide in treating patients with metastatic cancer.

Detailed Description
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OBJECTIVES: Primary Determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of docetaxel and temozolomide (TMZ) in patients with metastatic cancer. Secondary Determine the activity of docetaxel and TMZ in these patients. OUTLINE: This is a dose-escalation study. Patients receive docetaxel IV over 1 hour on days 1, 8, and 15 and oral temozolomide once daily on days 1-21. Treatment repeats every 28 days for up to 1 year in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of docetaxel and temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 6 patients receive treatment at the MTD. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Official Title
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Phase I Trial of Weekly Docetaxel and Daily Temozolomide in Patients With Metastatic Disease

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: docetaxel
* Drug: temozolomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed diagnosis of a nonhematologic malignancy that is refractory to standard therapy OR for which no standard therapy is available Measurable (by CT scan) or evaluable disease If palliative radiotherapy has been administered, the measurable disease must be outside the radiation port Prior brain metastasis allowed provided it was definitely treated with external-beam radiotherapy, gamma knife, or surgical resection and is clinically stable Repeat MRI or CT scans must demonstrate stabilization of disease 4 weeks after the definitive therapy is completed AND there must be no requirement for dexamethasone No active CNS metastasis PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 4 months Absolute granulocyte count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 8.0 g/dL (epoetin alfa and/or transfusions allowed) Creatinine ≤ 2 mg/dL Bilirubin normal PT normal, unless the patient is on warfarin for prior deep vein thrombosis or pulmonary embolus, requiring INR maintained at 2.0 - 3.0 Sodium and potassium normal AST and ALT ≤ 1.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN No decompensated cardiac arrhythmia or other severe cardiovascular disease (i.e., New York Heart Association [NYHA] class III-IV heart disease) Patients with clinically stable NYHA class III or IV heart disease require cardiac clearance No peripheral neuropathy > grade 1 No infection requiring IV antibiotics within the past 14 days No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 No HIV positivity No hepatitis B surface antigen or hepatitis C antibody positivity No pulmonary embolus within the past 3 weeks Not pregnant or nursing Negative pregnancy test Fertile patients must use 2 methods of effective contraception PRIOR CONCURRENT THERAPY: See Disease Characteristics No more than 3 courses of prior immunotherapy and/or chemotherapy for metastatic disease Interferon alfa in the adjuvant setting is not considered a course of prior therapy Patients who relapse on adjuvant interferon alfa must be off therapy for ≥ 3 weeks No prior stem cell or organ transplantation More than 21 days since prior immunotherapy or chemotherapy At least 21 days since prior hormonal therapy (except luteinizing hormone-releasing hormone [LHRH] agonists) or radiotherapy and recovered More than 21 days since prior surgery requiring general anesthesia No concurrent radiotherapy Concurrent LHRH agonist therapy allowed Concurrent physiologic replacement steroids allowed No other concurrent chemotherapy or thalidomide No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) during study chemotherapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: docetaxel|administered weekly in 5 escalating doses of 25 to 35 mg/ m(2) as a one-hour bolus intravenous infusion for 3 consecutive weeks.|
|Drug: temozolomide|administered orally daily for 3 weeks (escalating doses of 75 to 100 mg/m(2)). Cycles were repeated at 4 week intervals.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  | 4 cycles | 
| Dose-limiting toxicity |  | 4 cycles | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific