Gefitinib and Sirolimus in Treating Patients With Recurrent or Refractory Stage IIIB or Stage IV Non-Small Cell Lung Cancer
RATIONALE: Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as sirolimus, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to chemotherapy. Giving gefitinib together with sirolimus may reduce drug resistance and allow the tumor cells to be killed.
PURPOSE: This phase I/II trial is studying the side effects and best dose of sirolimus when given with gefitinib and to see how well they work in treating patients with recurrent or refractory stage IIIB or stage IV non-small cell lung cancer.
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Trial of ZD1839 (Iressa®) and Rapamycin (Rapamune) in Patients With Advanced Non Small Cell Lung Cancer|
- Maximum tolerated dose (Phase I) [ Designated as safety issue: Yes ]
- Overall response (complete response [CR] and partial response [PR]) as measured by RECIST criteria [ Designated as safety issue: No ]
- Disease control rate (CR, PR, and stable disease) correlated with smoking history [ Designated as safety issue: No ]
- Time to tumor progression and overall survival [ Designated as safety issue: No ]
- Quality of life as assessed by the Functional Assessment of Cancer Therapy-Lung (FACT-L) [ Designated as safety issue: No ]
- Lung cancer subscale from FACT-L [ Designated as safety issue: No ]
|Study Start Date:||October 2004|
- Determine the maximum tolerated dose of sirolimus when combined with gefitinib in patients with recurrent or refractory stage IIIB or IV non-small cell lung cancer.
- Determine the overall response rate (complete response [CR] and partial response [PR]) in patients treated with this regimen.
- Determine the disease control rate (CR, PR, and stable disease) in patients treated with this regimen.
- Determine the time to progression and overall survival of patients treated with this regimen.
- Determine the quality of life of patients treated with this regimen.
OUTLINE: This is an open-label, phase I, dose-escalation study of sirolimus followed by a phase II study.
- Phase I: Patients receive oral gefitinib once daily and oral sirolimus once daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.
Cohorts of 3-6 patients receive escalating doses of sirolimus 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.
- Phase II: Patients receive gefitinib and sirolimus as in phase I at the MTD. Quality of life is assessed at baseline, day 1 of each course, and then at 1 month post-progression.
Patients are followed every 9 weeks. Patients withdrawn from study treatment without evidence of disease progression are followed every 6 weeks until disease progression.
PROJECTED ACCRUAL: A total of 25 patients (11 for phase I and 14 for phase II) will be accrued for this study within 8.3 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00098462
|Study Chair:||Fairooz F. Kabbinavar, MD||Jonsson Comprehensive Cancer Center|