R115777 in Treating Patients With Advanced Solid Tumors

City of Hope

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Drug: tipifarnib

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00025454

U01CA062505 (U.S. NIH Grant/Contract)

P30CA033572 (U.S. NIH Grant/Contract)

CDR0000068963

CHNMC-PHI-33

NCI-4751

Details and patient eligibility

About

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 R115777 in treating patients who have advanced solid tumors.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose of R115777 in patients with advanced malignant solid tumors.
• Assess the toxicity of this drug in these patients.
• Determine, preliminarily, the efficacy of this drug in these patients.
• Determine the potential predictors of response in patients treated with drug.

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

Patients receive oral R115777 twice daily on weeks 1 and 3. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of R115777 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A minimum of 20 patients will be accrued for this study within 12 months.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant tumors deemed to be incurable or refractory to therapy

  • Advanced, recurrent, or metastatic disease

• Previously treated with at least 1 chemotherapy regimen

• Brain metastases allowed if asymptomatic and controlled (e.g., after prior surgical resection or radiotherapy/radiosurgery) and not on steroids or anticonvulsants

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,500/mm3
• Absolute granulocyte count at least 1,500/mm3
• Platelet count at least 75,000/mm3

Hepatic:

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

Renal:

• Creatinine clearance at least 60 mL/min OR
• Creatinine no greater than 1.6 mg/dL

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent biologic therapy

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosourea)

Endocrine therapy:

• See Disease Characteristics
• No concurrent hormonal therapy

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• No prior radiotherapy to a field containing a measurable target lesion unless there is evidence of progression or a new lesion is present
• No concurrent radiotherapy to measurable lesions

Surgery:

• See Disease Characteristics
• At least 3 weeks since prior major surgery and recovered

Other:

• At least 2 weeks since prior proton pump inhibitors (e.g., omeprazole)
• Concurrent H2 blockers (e.g., cimetidine or related drugs) or antacids are allowed if there is an interval of at least 2 hours between H2 blocker/antacid intake and R115777 dosing