A Pilot Study of Flavopiridol in Patients With Advanced Solid Tumors
A Pilot Study of Flavopiridol in Patients With Advanced Solid Tumors
This phase I trial is studying the side effects and best dose of alvocidib in treating patients with locally advanced or metastatic solid tumors. Drugs used in chemotherapy, such as alvocidib, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Alvocidib may also stimulate the immune system in different ways and stop tumor cells from growing. It may also stop the growth of solid tumors by blocking blood flow to the tumor.
PRIMARY OBJECTIVES:
I. Determine the toxicity profile and dose-limiting toxicity of flavopiridol (alvocidib) in patients with locally advanced or metastatic solid tumors.
II. Determine the maximum tolerated dose of this drug in these patients.
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.
II. Determine the immunomodulatory effects of this drug in these patients. III. Determine pharmacogenomics of this drug, using peripheral blood mononuclear cells, in patients who experience clinical response.
OUTLINE: This is a pilot, dose-escalation study.
Patients receive alvocidib intravenously (IV) over 4½ hours once weekly in weeks 1-4. Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease after 4 courses of therapy discontinue study treatment. Patients who achieve complete remission (CR) receive 1 additional course of therapy beyond documentation of CR. Cohorts of 3-6 patients receive escalating doses of alvocidib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 10 patients are treated at the MTD.
After completion of study treatment, patients are followed within 4 weeks.
Inclusion Criteria:
Histologically or cytologically confirmed solid tumor
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
No previously irradiated* measurable lesion unless lesion demonstrates progressive disease OR there are other measurable lesions outside the irradiated* field
The following are not considered measurable disease:
No uncontrolled brain metastases
Performance status - ECOG 0-1
At least 6 months
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
AST and ALT ≤ 2.5 times upper limit of normal (ULN)
Bilirubin ≤ 1.5 times ULN
Creatinine ≤ 1.5 times ULN
No symptomatic congestive heart failure
No unstable angina pectoris
No uncontrolled cardiac arrhythmia
No uncontrolled hypertension
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No history of allergic reaction attributed to compounds of similar chemical or biological composition to flavopiridol
No ongoing or active infection
No uncontrolled illness
No psychiatric illness or social situation that would preclude study compliance
More than 12 weeks since prior hepatic arterial chemoembolization
More than 4 weeks since prior systemic chemotherapy
No prior flavopiridol
See Disease Characteristics
More than 12 weeks since prior radioactive metaiodobenzylguanidine (MIBG)
More than 4 weeks since prior external beam radiotherapy
Recovered from all prior tumor-specific therapy
More than 4 weeks since prior investigational tumor-specific therapy
Concurrent octreotide for control of carcinoid syndrome allowed
No concurrent combination anti-retroviral therapy for HIV-positive patients
No other concurrent tumor-specific therapy
No other concurrent investigational therapy
No other concurrent anticancer therapy