Phase I Study of Flavopiridol in Combination With Cisplatin in Patients With Advanced Malignancies
18 Years
N/A
Both
Breast Cancer, Melanoma (Skin), Prostate Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
Phase I Study of Flavopiridol in Combination With Cisplatin in Patients With Advanced Malignancies
OBJECTIVES:
- Determine the maximum tolerated dose (MTD) of flavopiridol and cisplatin in patients
with advanced solid tumors. (Part 1)
- Determine the MTD of carboplatin when combined with flavopiridol in another group of
patients with advanced solid tumors. (Part 2)
- Determine the toxic effects of these regimens in this patient population.
- Determine the objective clinical response in patients treated with this regimen.
- Determine the pharmacokinetics of these regimens in this patient population.
OUTLINE: This is a dose-escalation study of flavopiridol and cisplatin (part 1), followed by
a dose-escalation study of carboplatin (part 2).
- Part 1: Patients receive flavopiridol IV over 24 hours. Two weeks later, patients
receive cisplatin IV over 2 hours immediately followed by flavopiridol IV over 24
hours. Treatment with cisplatin/flavopiridol continues every 3 weeks in the absence of
unacceptable toxicity or disease progression.
Sequential dose escalation of flavopiridol is followed by sequential dose escalation of
cisplatin. Cohorts of 3-6 patients receive escalating doses of flavopiridol and then
cisplatin until the maximum tolerated dose (MTD) of the combination is determined. The MTD
is defined as the dose preceding that at which at least 2 of 6 patients experience
dose-limiting toxicity.
- Part 2: Additional patients are accrued for part 2. Those patients receive carboplatin
IV over 30 minutes immediately followed by flavopiridol IV over 24 hours. Treatment
continues every 3 weeks in the absence of unacceptable toxicity or disease progression.
Cohorts of 3-6 patients receive escalating doses of carboplatin until the MTD is determined.
The MTD is defined as in part 1.
PROJECTED ACCRUAL: Approximately 36-48 patients will be accrued for this study within 2
years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed unresectable advanced solid tumor for which no standard
therapy exists that is potentially curative or definitely capable of extending life
expectancy
- Biopsy confirmation of recurrent tumors required, unless sole site of disease is
inaccessible bony and/or pulmonary metastases
- Eligible solid tumors include, but not are limited to, prostate cancer, breast
cancer, or melanoma
- No lymphoma
- No CNS metastases
- Patients with primary brain tumors are eligible if they are not receiving
antiepileptic medication(s) but are receiving stable doses of corticosteroids
- Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Sex:
- Not specified
Menopausal status:
- Not specified
Performance status:
- ECOG 0-2
Life expectancy:
- See Disease Characteristics
- At least 12 weeks
Hematopoietic:
- WBC at least 3,500/mm^3
- Absolute neutrophil count at least 1,700/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 8 g/dL
Hepatic:
- Bilirubin within upper limit of normal (ULN)
- AST and ALT no greater than 2.5 times ULN
- Alkaline phosphatase no greater than 2.5 times ULN
Renal:
- Creatinine no greater than 1.5 times ULN
Cardiovascular:
- No New York Heart Association class III or IV heart disease
- No history of angina
Neurologic:
- No grade 2 or greater peripheral neuropathy
- No seizure disorder
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No uncontrolled infection
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- More than 4 weeks since prior immunotherapy
- More than 4 weeks since prior biologic therapy
- No concurrent immunotherapy
Chemotherapy:
- More than 4 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas)
and recovered
- No other concurrent chemotherapy
Endocrine therapy:
- See Disease Characteristics
Radiotherapy:
- More than 4 weeks since prior radiotherapy
- No prior radiotherapy to more than 25% of bone marrow
- No concurrent radiotherapy
Surgery:
- See Disease Characteristics
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Keith C. Bible, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Federal Government
Study ID:
CDR0000066793
NCT ID:
NCT00003690
Start Date:
December 1998
Completion Date:
September 2003
Related Keywords:
- Breast Cancer
- Melanoma (Skin)
- Prostate Cancer
- Unspecified Adult Solid Tumor, Protocol Specific
- stage IV breast cancer
- recurrent breast cancer
- stage IV prostate cancer
- recurrent prostate cancer
- stage IV melanoma
- recurrent melanoma
- unspecified adult solid tumor, protocol specific
- Breast Neoplasms
- Melanoma
- Prostatic Neoplasms
- Neoplasms
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
