Chemotherapy Combined With Radiation Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: Phase I trial to study the effect on the body when combining irinotecan and cisplatin with radiation therapy in treating patients who have limited-stage small cell lung cancer that could not be completely removed during surgery.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of irinotecan administered with cisplatin and thoracic radiotherapy (given at two different schedules) in patients with limited stage small cell lung cancer. Determine the qualitative and quantitative toxicity and non-dose-limiting toxicity of these regimens in these patients. Determine the reversibility of all toxic effects associated with these regimens in these patients. OUTLINE: This is a non-randomized, dose-escalation study of irinotecan. Patients are assigned to 1 of 2 radiotherapy (RT) treatment groups. Radiotherapy: Group I: Patients undergo thoracic RT twice daily, 5 days a week, for 3 weeks. Group II: Patients undergo thoracic RT once daily, 5 days a week, for 7 weeks. Concurrent chemotherapy: Patients receive irinotecan IV over 60-90 minutes on days 1 and 8 and cisplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for 1 course for group I and 2 courses for group II. Post RT chemotherapy: Patients receive irinotecan and cisplatin as above for 3 courses for group I and 2 courses, beginning after RT is complete, for group II. Sequential cohorts of 6 patients per group receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 3 months for 1 year and then 6 months for 4 years. PROJECTED ACCRUAL: A total of 12-36 patients (6-18 per group) will be accrued for this study within 18 months.

Official Title
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Phase I Study of Irinotecan and Cisplatin in Combination With Twice Daily Thoracic Radiotherapy (45 Gy) or Once Daily Thoracic Radiotherapy (70 Gy) for Patients With Limited Stage Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: irinotecan hydrochloride
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed small cell lung cancer by one of two methods: Fine needle aspiration biopsy Two positive sputa Must have limited disease as defined by all of the following: Stage I-IIIB Confined to 1 hemithorax No T4 tumor based on malignant pleural or pericardial effusion Patients with pleural effusion too small to tap under CT guidance and not evident on chest x-ray are allowed No N3 disease based on contralateral hilar or contralateral supraclavicular involvement Measurable or evaluable disease Tumor must be able to be encompassed by specified radiotherapy fields without unacceptable risk of serious pulmonary compromise No complete tumor resection No pericardial effusion (regardless of cytology) PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 120,000/mm^3 Hepatic Bilirubin no greater than 1.5 mg/dL No known Gilbert's disease Renal Creatinine no greater than 1.5 mg/dL Cardiovascular No myocardial infarction within the past 6 months No symptomatic heart disease Pulmonary Forced expiratory volume (FEV)_1 at least 1.0 L/sec No uncontrolled bronchospasms No uncompensated chronic obstructive pulmonary disease Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No pre-existing peripheral neuropathy grade 2 or greater No other malignancy within the past 2 years except curatively treated basal or squamous cell skin cancer or carcinoma in situ of the bladder or cervix No other concurrent serious medical illness PRIOR CONCURRENT THERAPY: Biologic therapy No prior biologic therapy Chemotherapy No prior chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy No concurrent intensity-modulated radiotherapy Surgery See Disease Characteristics Other At least 7 days since prior enzyme-inducing anti-convulsant drugs (EIACDs) (e.g., phenytoin, carbamazepine, or phenobarbital) if used on a regular basis for more than 2 weeks Less than 2 weeks of regular use of EIACDs does not require a 7-day wash-out period At least 14 days since prior Hypericum perforatum (St. John's wort) No concurrent EIACDs No concurrent amifostine during chemoradiotherapy Concurrent gabapentin or other non-EIACDs allowed

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence A: Level 1<br>Irinotecan 40 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID | Drug: cisplatin<br> <br> Drug: irinotecan hydrochloride<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Sequence B: Level 1<br>Irinotecan 40 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily | Drug: cisplatin<br> <br> Drug: irinotecan hydrochloride<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Sequence A: Level 2<br>Irinotecan 50 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID | Drug: cisplatin<br> <br> Drug: irinotecan hydrochloride<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Sequence B: Level 2<br>Irinotecan 50 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily | Drug: cisplatin<br> <br> Drug: irinotecan hydrochloride<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Sequence A: Level 3<br>Irinotecan 60 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID | Drug: cisplatin<br> <br> Drug: irinotecan hydrochloride<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: Sequence B: Level 3<br>Irinotecan 60 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily | Drug: cisplatin<br> <br> Drug: irinotecan hydrochloride<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of irinotecan in combination with cisplatin and thoracic radiotherapy (45 Gy BID or 70 Gy daily) by toxicity assessment (Common Toxicity Criteria version 3.0) during acute and late toxicity |  | From the start of treatment until 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of non-dose limiting toxicity |  | From start of treatment to the end of follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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limited stage small cell lung cancer