Docetaxel and Temozolomide in Treating Patients With Metastatic Cancer

NeuroTherapia, Inc.

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: temozolomide

Drug: docetaxel

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00401180

CASE-CCF-4737

P30CA043703 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

25 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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