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.

Condition	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific	Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Drug: gemcitabine  Drug: tipifarnib	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose and dose limiting toxicities of R115777 in combination with gemcitabine in patients with advanced cancer. II. Investigate potential pharmacokinetic interactions between R115777 and gemcitabine in these patients. III. Determine the efficacy of this regimen in patients with measurable or evaluable disease. IV. Evaluate the quality of life of these patients.

PROTOCOL OUTLINE: This is a dose escalation study of R115777. Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and oral R115777 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 R115777 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 treatment.

PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Pathologically proven advanced cancer for which no curative therapy exists

--Prior/Concurrent Therapy--

Biologic therapy:

• No prior bone marrow transplantation
• No concurrent immunotherapy

Chemotherapy:

• 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

Endocrine therapy: No concurrent hormone therapy (except megestrol acetate)

Radiotherapy:

• 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)

Surgery: Not specified

Other:

• At least 30 days since prior investigational therapy
• No concurrent investigational therapy

--Patient Characteristics--

Age: 18 and over

Performance status: ECOG 0-2

Life expectancy: Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1500/mm3
• Platelet count greater than 100,000/mm3
• Hemoglobin greater than 9 g/dL

Hepatic:

• 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)

Renal: Creatinine normal

Other:

• Unassisted oral or enteral intake sufficient to maintain a reasonable state of nutrition
• No concurrent medical condition that is likely to interfere with study
• No active visual disturbances that require intervention beyond corrective lenses
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Texas
      San Antonio Cancer Institute, San Antonio,  Texas,  78229-3264,  United States

Study chairs or principal investigators

Eric Keith Rowinsky,  Study Chair,  San Antonio Cancer Institute   

Study ID Numbers:  CDR0000066815; UTHSC-9785011335; NCI-V98-1501; JRF-R115777-USA-4A; SACI-IDD-98-03
Record last reviewed:  July 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003707
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08