Flavopiridol Plus Cisplatin or Carboplatin in Treating Patients With Advanced Solid Tumors - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003690

Purpose

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 flavopiridol plus cisplatin or carboplatin in treating patients who have advanced solid tumors.

Condition	Intervention	Phase
Breast Cancer Melanoma (Skin) Prostate Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: alvocidib Drug: carboplatin Drug: cisplatin	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Phase I Study of Flavopiridol in Combination With Cisplatin in Patients With Advanced Malignancies

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Melanoma Prostate Cancer

Drug Information available for: Cisplatin Carboplatin Alvocidib Flavopiridol

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	48
Study Start Date:	December 1998

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003690

Locations

United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:

Keith C. Bible, MD, PhD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000066793, MAYO-950101, NCI-T97-0032
Study First Received:	November 1, 1999
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00003690 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Genital Neoplasms, Male
Prostatic Diseases
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Urogenital Neoplasms
Protein Kinase Inhibitors
Melanoma
Neoplasms by Site
Cisplatin
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Nevi and Melanomas
Growth Inhibitors

Breast Diseases
Neoplasms by Histologic Type
Skin Diseases
Growth Substances
Breast Neoplasms
Enzyme Inhibitors
Carboplatin
Genital Diseases, Male
Pharmacologic Actions
Neuroendocrine Tumors
Neuroectodermal Tumors
Flavopiridol
Neoplasms
Radiation-Sensitizing Agents
Prostatic Neoplasms

ClinicalTrials.gov processed this record on November 27, 2009