BMS-214662 in Treating Patients With Advanced Solid Tumors - Full Text View

Sponsor:	Dana-Farber Cancer Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00006242

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of BMS-214662 in treating patients who have advanced solid tumors.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: BMS-214662	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Trial of Farnesyltransferase Inhibitor BMS-214662 (NSC 710086) Escalating to a 24 Hour Continuous Intravenous Infusion in Patients With Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: BMS 214662

U.S. FDA Resources

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

Study Start Date:

November 2000

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose and dose-limiting toxicity of BMS-214662 in patients with advanced solid tumors.
Determine the safety of an appropriate dose of this drug for phase II studies.
Determine the pharmacokinetics of this drug in these patients.
Determine the extent and duration of farnesyltransferase inhibition in peripheral blood mononuclear cells and other relevant surrogate markers of pharmacological activity in patients treated with this drug.
Determine any preliminary evidence of antitumor activity of this drug in these patients.
Determine pharmacodynamic relationships for the pharmacological effect of this drug upon surrogate markers of activity and host toxicity in these patients.
Compare the toxicity profiles for the 1-hour vs 24-hour IV infusions of this drug in these patients.

OUTLINE: This is a dose-prolongation, dose-escalation study.

Single patient cohorts receive BMS-214662 IV over escalating periods of 2, 4, 8, 16, and 24 hours weekly for 3 weeks followed by 1 week of rest. If no patient experiences dose-limiting toxicity (DLT), dose escalation proceeds in the single patient cohorts.

Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Individual patient cohorts may increase their duration of BMS-214662 infusion in subsequent courses to the current duration safely reached.

Beginning with the infusion level at which DLT is first encountered by a single patient, cohorts of 3-6 patients receive escalating doses of BMS-214662 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 DLT. An additional cohort of 10 patients is treated at the MTD.

Patients are followed for at least 4 weeks.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 9-12 months.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of metastatic or inoperable malignancy for which no known curative or survival-prolonging palliative therapy exists or which has failed these therapies
No leukemia or primary CNS tumor
No active brain metastases, including cerebral edema by CT scan or MRI, progression from prior imaging study, requirement for steroids, or clinical symptoms

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-1

Life expectancy:

At least 2 months

Hematopoietic:

Absolute neutrophil count at least 1,500/mm3
Platelet count at least 100,000/mm3

Hepatic:

SGOT/SGPT no greater than 2.5 times upper limit of normal (ULN)
Bilirubin no greater than ULN

Renal:

Creatinine no greater than ULN
Creatinine clearance at least 50 mL/min
No known pre-existing renal disease

Cardiovascular:

No clinically significant atrial or ventricular arrhythmias
No second- or third-degree heart block or prolonged QTc interval (greater than 450 ms)

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No uncontrolled serious medical or psychiatric illness

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

At least 4 weeks since prior chemotherapy

Endocrine therapy:

See Disease Characteristics

Radiotherapy:

At least 4 weeks since prior radiotherapy
No concurrent radiotherapy

Surgery:

At least 3 weeks since prior major surgery

Other:

At least 7 days since prior substrates of cytochrome P450-3A4 (CYP3A4), including terfenadine, astemizole, triazolam, midazolam, cisapride, bepridil, rifabutin, simvastatin, lovastatin, and propafenone
No substrates of CYP3A4 during and for at least 1 week after study
No non-steroidal anti-inflammatory drugs or other potentially nephrotoxic medications for at least 2 days before, during, and for at least 2 days after study drug administration

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006242

Locations

United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Dana-Farber Cancer Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Joseph Paul Eder, MD

Dana-Farber Cancer Institute

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:	CDR0000068170, DFCI-00003, NCI-67
Study First Received:	September 11, 2000
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00006242 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Neoplasms

ClinicalTrials.gov processed this record on November 09, 2009