BMS-214662 in Treating Patients With Advanced Solid Tumors

NCT00006242 | Completed Phase 1

• 4 other identifiers: NCI-2013-0003200-003U01CA062490CDR0000068170
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD) of BMS-214662, based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0

  Up to 28 days

• Adverse events, based on the NCI CTC v2.0

  Up to 5 years

• Plasma concentration-time profile of BMS-214662 when given as a continuous IV infusion escalating to 24 hr

  Up to 48 hours

Secondary Outcomes (4)

• Determination whether the pharmacokinetic behavior is linear as dose is escalated

  Up to 48 hours

• Determination of dose that provides potentially effective level of systemic exposure to the drug as indicated by information from preclinical studies

  Up to 48 hours

• Interpatient variability in the steady state plasma concentration (C^ss) and other pharmacokinetic variables in patients treated at the MTD peak

  Up to 48 hours

• Correlations between pharmacokinetic variables and pretreatment laboratory values, toxicity, and indications of biological response (farnesyltransferase activity)

  Up to 48 hours

Study Arms (1)

Treatment (BMS-214662)

EXPERIMENTAL

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 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.

Drug: BMS-214662; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

BMS-214662 DRUG

Given IV

Also known as: farnesyltransferase inhibitor BMS-214662, FTI BMS 214662

Treatment (BMS-214662)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (BMS-214662)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (BMS-214662)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic or inoperable malignancy, other than leukemia or a primary CNS tumor, for which there is no known curative or survival prolonging palliative therapy, or failure of these therapies
• Life expectancy \>= 2 months
• ECOG performance status 0-1
• ANC \>= 1,500/mm\^3
• Platelets \>= 100,000/mm\^3
• SGOT and SGPT =\< 2.5 times the upper limit of normal (ULN)
• Total bilirubin =\< ULN
• Serum creatinine =\< ULN
• Calculated or measured creatinine clearances (Cockcroft-Gault formula) \>= 50 ml/minute
• \>= 3 weeks since major surgery
• \>= 4 weeks since chemotherapy or radiation therapy
• No uncontrolled serious medical or psychiatric illness
• Women of childbearing potential must not be pregnant or lactating; all women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L of beta-HCG) within 72 hr prior to receiving the study medication; BMS 214662 has antiproliferative effects which may be harmful to the developing fetus or nursing infant
• Fertile males and females must use adequate contraception
• Signed informed consent

You may not qualify if:

• Any history of clinically significant atrial or ventricular arrhythmias, any history of second or third degree heart block, or prolonged QTc interval (greater than 450 ms) on electrocardiogram
• Active brain metastases including evidence of cerebral edema by CT scan or MRI, or progression from prior imaging study, any requirement for steroids, or clinical symptoms of/from brain metastases
• Received any drugs within 7 days prior to receiving study drug therapy, which are known to be substrates of cytochrome P450-3A4 (CYP3A4)
• Patients should not receive concurrent therapy with known CYP3A4 substrates while on study and for at least 1 week following the last dose of BMS-214662; this is due to the CYP3A4 inhibitory potential of BMS-214662; a representative list of commonly prescribed known CYP3A4 substrates includes: terfenadine, astemizole, triazolam, midazolam, cisapride, bepridil, rifabutin, simvastatin, lovastatin, and propafenone
• Patients receiving therapy with BMS-214662 should not receive concomitant therapy with NSAIDs or other potentially nephrotoxic medications for at least 2 days before and after administration of BMS-214662
• Patients with known pre-existing renal disease are not eligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Interventions

7-cyano-2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine

Study Officials

• Joseph Eder

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2000
• First Posted: May 22, 2003
• Study Start: July 1, 2000
• Primary Completion: September 1, 2005
• Last Updated: February 1, 2013

Record last verified: 2013-01

Locations

US (1)