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 effectiveness of combination chemotherapy and radiation therapy in treating patients who have locally advanced non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
stage IIIA non-small cell lung cancer stage II non-small cell lung cancer stage IIIB non-small cell lung cancer recurrent non-small cell lung cancer	Drug: cisplatin  Drug: irinotecan	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose of irinotecan when administered with cisplatin and radiotherapy in patients with locally advanced non-small cell lung carcinoma. II. Determine the toxic effects, especially acute and long-term esophagitis and pneumonitis, of this regimen in these patients. III. Determine the response rate, duration to progression, and sites of relapse in patients treated with this regimen.

PROTOCOL OUTLINE: This is a multicenter, dose-escalation study of irinotecan. Patients receive irinotecan IV over 90 minutes and cisplatin over 1 hour on day 1. Patients also undergo radiotherapy once daily on days 1-5. Treatment repeats every 7 days for 7 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients 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 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 3-27 patients will be accrued for this study within 3 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC); Stage IIIB or bulky stage IIIA not amenable to surgical resection; Medically inoperable stage II or non-bulky stage IIIA; Locally recurrent disease following surgery that is not amenable to further surgical resection
• No small cell carcinoma or mixed cytology
• No disease beyond radiation portal (T4 tumors with documented multifocal malignant pleural involvement or extension of supraclavicular nodal disease to cervical chain)
• No pleural effusion; Pleural effusions visible on CT scan but not on chest x-ray that are inaccessible to thoracentesis or are cytologically negative are allowed
• Ineligible for enrollment on protocol RTOG 93-09

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy for NSCLC; No prior irinotecan or topotecan
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiotherapy for NSCLC; No prior radiotherapy to the chest
• Surgery: See Disease Characteristics
• Other: No concurrent phenytoin, phenobarbital, or other antiepileptic prophylaxis

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2; Karnofsky 50-100%
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 2,000/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 1.5 mg/dL; No known Gilbert's disease
• Renal: Creatinine no greater than 1.5 mg/dL; Calcium less than 12.0 mg/dL
• Cardiovascular: No symptomatic cardiovascular disease; No active angina No congestive heart failure requiring active therapy; No uncontrolled arrhythmias; No myocardial infarction within the past 6 months
• Pulmonary: FEV1 at least 1.0 L unless cleared by radiation oncologist
• Other: Not pregnant; Negative pregnancy test; Fertile patients must use effective contraception for 3 months before study, during study, and for 3 months after study; HIV negative; No other concurrent active or invasive malignancy except nonmelanoma skin cancer; Less than 10% unintended weight loss within 3 months of diagnosis; No other concurrent medical condition that would preclude study; No social situation or psychiatric disorder that would preclude study; No active or uncontrolled infection; No history of seizures; No uncontrolled diabetes mellitus (random blood sugar at least 250 mg/dL)

New Jersey
      Community Medical Center, Toms River,  New Jersey,  08755,  United States
      Fox Chase Cancer Center at Virtua Memorial Hospital Burlington County, Mount Holly,  New Jersey,  08060,  United States
      Riverview Medical Center - Booker Cancer Center, Red Bank,  New Jersey,  07701,  United States
      South Jersey Regional Cancer Center, Millville,  New Jersey,  08332,  United States
      St. Francis Medical Center, Trenton,  New Jersey,  08629,  United States
Pennsylvania
      Delaware County Memorial Hospital, Drexel Hill,  Pennsylvania,  19026,  United States
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States
      Reading Hospital and Medical Center, Reading,  Pennsylvania,  19612-6052,  United States

Study chairs or principal investigators

Corey Jay Langer,  Study Chair,  Fox Chase Cancer Center   

Study ID Numbers:  CDR0000068803; FCCC-98020; NCI-G01-1995
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  August 10, 2001
ClinicalTrials.gov Identifier:  NCT00022308
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08