BMS-214662 in Treating Patients With Solid Tumors

Study Overview
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Brief Summary
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Phase I trial to study the effectiveness of BMS-214662 in treating patients who have solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die

Detailed Description
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OBJECTIVES: I. Determine the maximum tolerated dose of BMS-214662 in patients with solid tumors. II. Evaluate intermediate biological endpoints as surrogates for the effectiveness of this drug in these patients. III. Determine the nature of dose limiting toxicity of this drug in this patient population. IV. Determine the recommended phase II regimen of this drug in these patients. V. Establish a pharmacologic and pharmacokinetic profile of this drug in these patients. OUTLINE: This is a dose escalation study. Patients receive BMS-214662 IV over 1 hour on days 1, 8, 15, and 22. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. 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 at which 2 of 6 patients experience dose limiting toxicities. Patients are followed every 3 months for at least 24 months.

Official Title
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Phase I Study of Farnesyl Transferase Inhibitor BMS-214662 (NSC 710086D) in Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific, Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: BMS-214662
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of malignant solid tumor for which a standard curative therapy does not exist Performance status - Karnofsky 70-100% At least 6 months WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10.0 g/dL Bilirubin no greater than 2.0 mg/dL AST no greater than 2 times upper limit of normal Albumin at least 3.0 g/dL Creatinine no greater than 1.5 mg/dL No uncontrolled heart disease No history of clinically significant cardiac arrhythmia that could be exacerbated by QT interval prolongation Corrected QT interval no greater than 450 milliseconds Must not require total parenteral nutrition No manifestations of malabsorption syndrome due to prior surgery, gastrointestinal disease, or unknown reasons Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No signs or symptoms of acute infection requiring systemic therapy No grade 3 or 4 neurotoxicity from prior anticancer treatment or neuropathy from any cause No confusion, disorientation, or psychiatric illness that may preclude study No more than 3 prior chemotherapy regimens At least 4 weeks since prior chemotherapy (6 weeks since prior nitrosoureas or mitomycin) and recovered No other concurrent antineoplastic agents No concurrent hormonal anticancer therapy At least 4 weeks since prior radiotherapy No concurrent radiotherapy Prior drugs known to prolong the QT interval allowed if they can be safely discontinued for a time period equal to 4 elimination half-lives prior to administering study drug No drugs known to prolong the QT interval during and for 24 hours after study drug No concurrent therapy with known CYP3A4 substrates No other concurrent investigational agents
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Patients receive BMS-214662 IV over 1 hour on days 1, 8, 15, and 22. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. | Drug: BMS-214662<br>* Given IV<br>* Other names: FTI BMS 214662;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD, defined as the dose level among the 9 levels studied having toxicity rate closest to a target of 33%, graded according to CTC version 2.0 | Toxicity is defined as grade 3, 4 non-hematologic and grade 4 hematologic (neutropenia and thrombocytopenia) toxicity. The continual reassessment method (CRM) will be used. | Up to 6 weeks |