Docetaxel and Temozolomide in Treating Patients With Metastatic Cancer

NCT ID: NCT00401180

Last Updated: 2011-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-06-30
• Study Completion Date: 2008-07-31

Brief Summary

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

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

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.

Intervention Type: DRUG

temozolomide

administered orally daily for 3 weeks (escalating doses of 75 to 100 mg/m(2)). Cycles were repeated at 4 week intervals.

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Cleveland Clinic Taussig Cancer Institute

Principal Investigators

Ronald M. Bukowski, MD

Role: STUDY_CHAIR

The Cleveland Clinic

Locations

Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

References

Tamaskar I, Mekhail T, Dreicer R, Olencki T, Roman S, Elson P, Bukowski RM. Phase I trial of weekly docetaxel and daily temozolomide in patients with metastatic disease. Invest New Drugs. 2008 Dec;26(6):553-9. doi: 10.1007/s10637-008-9153-0. Epub 2008 Jul 15.

Reference Type: RESULT

PMID: 18626572 (View on PubMed)

Other Identifiers

P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CASE-CCF-4737

Identifier Type: -

Identifier Source: secondary_id

CASE-CCF-4737

Identifier Type: -

Identifier Source: org_study_id