Clinical trial NCT00016185: Flavopiridol and Docetaxel in Treating Patients With Advanced Solid Tumors
Official title: Phase I Study Of Flavopiridol And Docetaxel (Taxotere) In Patients With Advanced Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
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 and docetaxel in treating patients who have advanced solid tumors.

Detailed description: OBJECTIVES:

* Determine the dose-limiting toxic effects and maximum tolerated dose of flavopiridol and docetaxel in patients with advanced solid tumors.
* Determine the objective response rate and duration of response in patients treated with this regimen.
* Determine the pharmacokinetics of these drugs in this patient population.

OUTLINE: This is a dose-escalation study.

Patients receive docetaxel IV over 60 minutes on day 1 and flavopiridol IV continuously over 24 hours on day 2. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of docetaxel and flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study within 9-11 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed metastatic or unresectable solid tumor

  * No standard relatively effective curative or palliative measures exist
* Measurable disease in at least 1 dimension

  * At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
* No known clinically active and uncontrolled brain metastases

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2
* Karnofsky 60-100%

Life expectancy:

* More than 12 weeks

Hematopoietic:

* WBC at least 3,000/mm\^3
* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin normal
* ALT/AST no greater than 1.5 times upper limit of normal (ULN)
* Alkaline phosphatase no greater than 2.5 times ULN

Renal:

* Creatinine normal

Cardiovascular:

* No symptomatic congestive heart failure
* No unstable angina pectoris
* No cardiac arrhythmia

Other:

* No prior allergic reactions to compounds of similar chemical or biologic composition to flavopiridol or docetaxel
* No other uncontrolled concurrent illness that would preclude study participation
* No ongoing or active infection
* No psychiatric illness or social situations that would preclude study compliance
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No concurrent immunotherapy

Chemotherapy:

* At least 6 months since prior taxane therapy
* At least 4 weeks since other prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
* No other concurrent chemotherapy

Endocrine therapy:

* No concurrent hormonal therapy except contraceptives, appetite stimulants, or replacement steroids

Radiotherapy:

* At least 4 weeks since prior radiotherapy and recovered
* No concurrent radiotherapy

Surgery:

* See Disease Characteristics

Other:

* No other concurrent investigational agents
* No concurrent combination antiretroviral therapy for HIV-positive patients

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Philip A. Philip, MD, PhD, FRCP
role: STUDY_CHAIR
References:
citation: El-Rayes BF, Gadgeel S, Parchment R, Lorusso P, Philip PA. A phase I study of flavopiridol and docetaxel. Invest New Drugs. 2006 Jul;24(4):305-10. doi: 10.1007/s10637-005-4343-5.
citation: Patel B, El-Rayes BF, Gadgeel SM, et al.: A phase I study of flavopiridol and docetaxel. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-932, 2003.