Clinical trial NCT00045448: Combination Chemotherapy in Treating Patients With Advanced Solid Tumors
Official title: Single Center Open-Label Non-Comparative Phase I Dose Finding Study Of Weekly Flavopiridol In Combination With Weekly Docetaxel In Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining flavopiridol with docetaxel in treating patients who have advanced solid tumors.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose of flavopiridol when administered in combination with 2 different doses of docetaxel in patients with advanced solid tumors.
* Determine the clinical pharmacokinetics of this regimen in these patients.
* Determine, preliminarily, the therapeutic activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of flavopiridol.

Patients receive docetaxel IV over 30 minutes followed at least 4 hours later by flavopiridol IV over 1 hour on days 1, 8, and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Separate MTDs of flavopiridol are determined when flavopiridol is combined with 2 different doses of docetaxel. A total of 10 patients are treated at each flavopiridol MTD.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 6-56 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed advanced solid tumor that is refractory to standard therapy or for which no standard therapy exists
* Measurable or evaluable disease
* No symptomatic or untreated CNS metastases or primary CNS neoplasm

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Karnofsky 70-100%

Life expectancy

* Not specified

Hematopoietic

* WBC at least 3,500/mm3
* Absolute neutrophil count at least 1,500/mm3
* Platelet count at least 100,000/mm3
* Hemoglobin at least 8 g/dL

Hepatic

* Bilirubin no greater than upper limit of normal (ULN)
* SGOT/SGPT no greater than 2.5 times ULN if alkaline phosphatase no greater than ULN OR
* Alkaline phosphatase no greater than 2.5 times ULN if SGOT/SGPT no greater than ULN

Renal

* Creatinine no greater than 1.5 mg/dL

Cardiovascular

* No history of cardiac arrhythmias
* No congestive heart failure
* No myocardial infarction within the past 6 months

Other

* No concurrent serious or uncontrolled infection
* No diabetes not adequately controlled with medication
* No peripheral neuropathy greater than grade 1
* No known allergy to docetaxel or other medications formulated in Polysorbate 80
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 2 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy

* At least 4 weeks since prior immunotherapy

Chemotherapy

* At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
* Prior taxanes allowed
* No prior flavopiridol

Endocrine therapy

* At least 4 weeks since prior hormonal therapy

Radiotherapy

* At least 4 weeks since prior radiotherapy

Surgery

* Not specified

Other

* Recovered from prior therapy
* No prior enrollment in this study

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Gary K. Schwartz, MD
role: STUDY_CHAIR
References: