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
Overview
- Phase
- Phase 1
- Intervention
- cisplatin
- Conditions
- Lung Cancer
- Sponsor
- Radiation Therapy Oncology Group
- Enrollment
- 36
- Locations
- 49
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Sequence A: Level 1
Irinotecan 40 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID
Intervention: cisplatin
Sequence A: Level 1
Irinotecan 40 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID
Intervention: irinotecan hydrochloride
Sequence A: Level 1
Irinotecan 40 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID
Intervention: radiation therapy
Sequence B: Level 1
Irinotecan 40 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily
Intervention: cisplatin
Sequence B: Level 1
Irinotecan 40 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily
Intervention: irinotecan hydrochloride
Sequence B: Level 1
Irinotecan 40 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily
Intervention: radiation therapy
Sequence A: Level 2
Irinotecan 50 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID
Intervention: cisplatin
Sequence A: Level 2
Irinotecan 50 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID
Intervention: irinotecan hydrochloride
Sequence A: Level 2
Irinotecan 50 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID
Intervention: radiation therapy
Sequence B: Level 2
Irinotecan 50 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily
Intervention: cisplatin
Sequence B: Level 2
Irinotecan 50 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily
Intervention: irinotecan hydrochloride
Sequence B: Level 2
Irinotecan 50 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily
Intervention: radiation therapy
Sequence A: Level 3
Irinotecan 60 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID
Intervention: cisplatin
Sequence A: Level 3
Irinotecan 60 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID
Intervention: irinotecan hydrochloride
Sequence A: Level 3
Irinotecan 60 mg/m2, cisplatin 60 mg/m2, concurrent radiation therapy (RT) at 1.5 Gy BID
Intervention: radiation therapy
Sequence B: Level 3
Irinotecan 60 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily
Intervention: cisplatin
Sequence B: Level 3
Irinotecan 60 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily
Intervention: irinotecan hydrochloride
Sequence B: Level 3
Irinotecan 60 mg/m2, cisplatin 60 mg/m2, concurrent RT at 2 Gy once daily
Intervention: radiation therapy
Outcomes
Primary Outcomes
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
Time Frame: From the start of treatment until 90 days
Secondary Outcomes
- Rate of non-dose limiting toxicity(From start of treatment to the end of follow-up)