Combination Chemotherapy in Treating Patients With Advanced Cancer

A Phase I, Maximum Tolerated Dose (MTD) Trial to Determine the Safety and Pharmacokinetics of Chronic Oral Administration of Farnesyl Transferase Inhibitor R115777 in Combination With Gemcitabine in Subjects With Advanced Incurable Cancer

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: gemcitabine hydrochloride; Drug: tipifarnib

Detailed Description

OBJECTIVES:

• 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 disease.
• 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 treatment.

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

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Pathologically proven advanced cancer for which no curative therapy exists

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3
• 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 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:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Eric K. Rowinsky, MD, San Antonio Cancer Institute

Study record dates

Study Major Dates

• Study Start: October 1, 1998
• Primary Completion (Actual): November 1, 2002
• Study Completion (Actual): November 1, 2002

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: July 14, 2003
• First Posted (Estimate): July 15, 2003

Study Record Updates

• Last Update Posted (Estimate): June 28, 2012
• Last Update Submitted That Met QC Criteria: June 26, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Tipifarnib
• Other Study ID Numbers: CDR0000066815; P30CA054174 (U.S. NIH Grant/Contract); UTHSC-9785011335 (Other Identifier: UTHSCSA IRB); JRF-R115777-USA-4A (Other Identifier: Johnson and Johnson); SACI-IDD-98-03 (Other Identifier: San Antonio Cancer Institute); NCI-V98-1501 (Other Identifier: NCI)