Phase I Trial of R115777 and OSI-774 in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Erlotinib Hydrochloride
- Conditions
- Solid Neoplasm
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 29
- Locations
- 1
- Primary Endpoint
- Incidence of all adverse events, graded according to the National Cancer Institute Common (NCI) Terminology Criteria for Adverse Events (CTCAE) version 3.0
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
This phase I trial studies the side effects and best dose of tipifarnib and erlotinib hydrochloride in treating patients with solid tumors that have spread to other places in the body. Tipifarnib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the maximal tolerated dose of R115777 (tipifarnib) in combination with OSI-774 (erlotinib hydrochloride). II. To describe the toxicity profile of this combination. III. To evaluate the effect of OSI-774 on the disposition of R115777. IV. To evaluate in vitro markers of farnesyl transferase (FT) inhibition and epidermal growth factor receptor (EGFR) inhibition. OUTLINE: This is a dose-escalation study. Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-28 (days 8-28 of course 1 as of 11/4/2013) and tipifarnib PO twice daily (BID) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. (Closed to accrual as of 2/2/06) After completion of study treatment, patients are followed up at 3 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologic proof of cancer that is unresectable and for which no standard life-prolonging therapy is available
- •Absolute neutrophil count (ANC) \>= 1500/uL
- •Platelet count (PLT) \>= 100,000/uL
- •Total bilirubin =\< 2 mg/dL
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN)
- •Creatinine =\< 1.5 x ULN
- •Hemoglobin (Hgb) \>= 9.0 g/dL
- •Ability to provide informed consent
- •Willingness to return to Mayo Clinic Rochester for follow up
- •Life expectancy \>= 12 weeks
Exclusion Criteria
- •Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2, 3, or 4
- •Uncontrolled infection
- •Any of the following prior therapies:
- •Chemotherapy =\< 4 weeks prior to study entry
- •Mitomycin C/nitrosoureas =\< 6 weeks prior to study entry
- •Immunotherapy =\< 4 weeks prior to study entry
- •Biologic therapy =\< 4 weeks prior to study entry
- •Hormonal cancer therapy =\< 4 weeks prior to study entry
- •Radiation therapy =\< 4 weeks prior to study entry
Arms & Interventions
Treatment (erlotinib hydrochloride, tipifarnib)
Patients receive erlotinib hydrochloride PO QD on days 1-28 (days 8-28 of course 1 as of 11/4/2013) and tipifarnib PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. (Closed to accrual as of 2/2/06)
Intervention: Erlotinib Hydrochloride
Treatment (erlotinib hydrochloride, tipifarnib)
Patients receive erlotinib hydrochloride PO QD on days 1-28 (days 8-28 of course 1 as of 11/4/2013) and tipifarnib PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. (Closed to accrual as of 2/2/06)
Intervention: Laboratory Biomarker Analysis
Treatment (erlotinib hydrochloride, tipifarnib)
Patients receive erlotinib hydrochloride PO QD on days 1-28 (days 8-28 of course 1 as of 11/4/2013) and tipifarnib PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. (Closed to accrual as of 2/2/06)
Intervention: Pharmacological Study
Treatment (erlotinib hydrochloride, tipifarnib)
Patients receive erlotinib hydrochloride PO QD on days 1-28 (days 8-28 of course 1 as of 11/4/2013) and tipifarnib PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. (Closed to accrual as of 2/2/06)
Intervention: Tipifarnib
Outcomes
Primary Outcomes
Incidence of all adverse events, graded according to the National Cancer Institute Common (NCI) Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time Frame: Up to 30 days after last study treatment
The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.
Incidence of toxicity graded according to NCI CTCAE version 3.0
Time Frame: Up to 3 months
Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
Secondary Outcomes
- Best response as assessed by the Response Evaluation Criteria in Solid Tumors(Start of the treatment until disease progression/recurrence, assessed up to 3 months)
- Time until any treatment related toxicity(Up to 30 days after last study treatment)
- Time until hematologic nadirs (white blood cells, ANC, platelets)(Up to 3 months)
- Time until treatment related grade 3+ toxicity(Up to 30 days after last study treatment)
- Time to treatment failure(Time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months)
- Time to progression(Up to 3 months)