Clinical trial NCT00401180: Docetaxel and Temozolomide in Treating Patients With Metastatic Cancer
Official title: Phase I Trial of Weekly Docetaxel and Daily Temozolomide in Patients With Metastatic Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-11-17
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Maximum tolerated dose
timeFrame: 4 cycles
measure: Dose-limiting toxicity
timeFrame: 4 cycles
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Ronald M. Bukowski, MD
role: STUDY_CHAIR
References:
citation: 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.