Tipifarnib Plus Radiation Therapy After Combination Chemotherapy in Treating Patients With Stage III Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by making tumor cells more sensitive to radiation therapy. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing and may also make tumor cells more sensitive to radiation therapy. PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib when given together with radiation therapy after combination chemotherapy in treating patients with stage III non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose and dose-limiting toxicity of tipifarnib given concurrently with radiotherapy after induction chemotherapy comprising paclitaxel and carboplatin and followed by maintenance therapy with tipifarnib in patients with stage IIIA or IIIB non-small cell lung cancer. Determine the tumor response at 3 months in patients treated with this regimen. OUTLINE: This is multicenter, dose-escalation study of tipifarnib. Patients receive induction chemotherapy comprising carboplatin IV over 30 minutes on day 1 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses. Beginning 4-6 weeks after the completion of induction chemotherapy, patients receive oral tipifarnib twice daily for 7 weeks. Patients undergo radiotherapy once daily 5 days a week for 7 weeks beginning 3 days after the start of tipifarnib. After completion of radiotherapy, patients receive oral tipifarnib twice daily for 4 days and then once daily for 4 days. Cohorts of 3-6 patients receive escalating doses of tipifarnib while receiving radiotherapy 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. Beginning 4-6 weeks after the completion of radiotherapy and tipifarnib, patients receive maintenance therapy comprising oral tipifarnib twice daily on days 1-21. Maintenance therapy repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed at 3, 6, and 12 months. PROJECTED ACCRUAL: Approximately 9-12 patients will be accrued for this study within 1 year.

Official Title
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A Phase I Trial of Farnesyltransferase Inhibitor, R115777 (NSC # 702818) and Radiotherapy in Patients With Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: paclitaxel
* Drug: tipifarnib
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed non-small cell lung cancer Locally advanced (stage IIIA or IIIB) disease requiring radiotherapy No malignant pleural effusion PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 mg/dL No grade 2 or greater elevation of liver function tests Renal: Creatinine no greater than 1.5 times normal Pulmonary: FEV_1 at least 600 cc Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No grade 3 or 4 peripheral neuropathy No known allergy to imidazole drugs (e.g., ketoconazole, miconazole, econazole, or terconazole) PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Up to 2 prior or concurrent carboplatin and paclitaxel chemotherapy regimens allowed Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics No prior thoracic radiotherapy Surgery: At least 3 weeks since prior exploratory thoracotomy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carboplatin|nan|
|Drug: paclitaxel|nan|
|Drug: tipifarnib|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer