RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
so they stop growing or die. Combining more than one drug may kill more cancer cells.
PURPOSE: Phase I trial to study the effectiveness of combining R115777 with gemcitabine in
treating patients with advanced cancer.
- Determine the maximum tolerated dose and dose limiting toxicities of tipifarnib in
combination with gemcitabine in patients with advanced cancer.
- Investigate potential pharmacokinetic interactions between tipifarnib and gemcitabine
in these patients.
- Determine the efficacy of this regimen in patients with measurable or evaluable
- Evaluate the quality of life of these patients.
OUTLINE: This is a dose-escalation study of tipifarnib.
Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and oral tipifarnib
every 12 hours beginning on day 2. Treatment continues every 4 weeks in the absence of
disease progression or unacceptable toxicity.
Cohorts of 3-6 patients each receive escalating doses of tipifarnib until the maximum
tolerated dose (MTD) is reached. The MTD is defined as the dose at which fewer than one
third of the patients experience dose limiting toxicity.
Quality of life is assessed before treatment, on day 22 of each course, and at the end of
PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study.
- Pathologically proven advanced cancer for which no curative therapy exists
- 18 and over
- ECOG 0-2
- Not specified
- Absolute neutrophil count greater than 1,500/mm^3
- Platelet count greater than 100,000/mm^3
- Hemoglobin greater than 9 g/dL
- Bilirubin normal
- SGOT and SGPT no greater than 2 times upper limit of normal (ULN) (no greater than 5
times ULN if liver metastases present)
- Creatinine normal
- Unassisted oral or enteral intake sufficient to maintain a reasonable state of
- No concurrent medical condition that is likely to interfere with study participation
- No active visual disturbances that require intervention beyond corrective lenses
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- No prior bone marrow transplantation
- No concurrent immunotherapy
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- No prior high dose chemotherapy with bone marrow or stem cell rescue
- No other concurrent chemotherapy
- No concurrent hormone therapy (except megestrol acetate)
- At least 4 weeks since prior radiotherapy
- No prior radiotherapy to 25% or more of bone marrow
- No concurrent radiotherapy (except palliative radiotherapy within the first 28 days
of the study)
- Not specified
- At least 30 days since prior investigational therapy
- No concurrent investigational therapy