Phase I Study of Iressa and CRT/IMRT in Chinese Patients With IIIB/IV NSCLC After Failure of Platinum-Based Chemotherapy
Recruitment status was: Recruiting
The primary objective of this study is to evaluate the tolerability and the maximum tolerated dose of Conformal or Intensity-Modulated Radiotherapy when given in combination with gefitinib 250mg in Chinese patients with IIIB or IV NSCLC after failure of platinum-based chemotherapy.
Secondary objectives of the study are to obtain the preliminary information on efficacy after concomitant treatment of gefitinib 250mg and radiotherapy in Chinese patients with IIIB or IV NSCLC after failure of platinum-based chemotherapy, as measured by RECIST criteria.
To determine the pattern of failure (e.g., local, regional, or distant metastasis) in patients treated with this regimen.
Carcinoma, Non-Small-Cell Lung
Device: Radiation Therapy
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Iressa and CRT/IMRT in Chinese Patients With IIIB/IV NSCLC After Failure of Platinum-Based Chemotherapy|
- Dose-limiting toxicities per protocol [ Time Frame: 3, 6 and 12 months ] [ Designated as safety issue: Yes ]
- Response rate, mortality [ Time Frame: 3, 6 and 12 months ] [ Designated as safety issue: Yes ]
- Pattern of failure(e.g., local, regional, or distant metastasis) [ Time Frame: 3, 6 and 12 months ] [ Designated as safety issue: No ]
|Study Start Date:||July 2007|
|Estimated Study Completion Date:||October 2009|
|Estimated Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
Thoracic RT for patients will start from 54Gy, and then escalate dose at 2Gy increment to 60Gy. At each dose level, 8 patients are required to complete RT without dose limiting toxicity(DLT). Evaluation will be done after 8 patients have completed the treatment.If there are >=2 DLT in the first 8 patients, the maximum tolerated dose (MTD) is achieved. If there is a single DLT revealed, an additional 8 patients will be recruited to that dose level. Should there be severe complication occurred again be at least 1 more DLT, then MTD is thought to be achieved.Hence,MTD will be achieved if at least 2 out of the first 8 patients have a DLT,or if a further 8 patents are recruited, >=2 out of 16 patients have a DLT. Concurrent with RT, patients will be given gefitinib 250 mg/day PO as well as same dose PO for 60 days after the completion of RT.
gefitinib 250 mg/day,PO concurrent with RT and 250 mg/day,PO for 60 days after the completion of RT.
Other Name: Iressa@Device: Radiation Therapy
group 1.54Gy/27Fx concurrent with gefitinib group 2.56Gy/28Fx concurrent with gefitinib group 3.58Gy/29Fx concurrent with gefitinib group 4.60Gy/30Fx concurrent with gefitinib
Other Name: 3-D CRT and IMRT
Laboratory research has suggested that targeting specific signalling proteins would be well suited for selectively enhancing the tumor radiosensitivity. In human xenograft models (non-small cell lung cancer and breast cancer) treated with gefitinib and irradiation, combined therapy has shown a significant increase in tumor growth delay as compared with monotherapy of irradiation or gefitinib. The epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 selectively potentiates radiation response of human tumors in nude mice, with a marked improvement in therapeutic index. The authors concluded that gefitinib profoundly enhanced the antitumor action of RT against the tested tumors without significant adverse effects, increasing the therapeutic selectively of ionizing radiation in certain model systems. Substantial benefits for this multimodality therapy in patients could be expected.
While there are no published data on the feasibility and efficacy of combined gefitinib and radiation therapy in Chinese population who might be susceptible to gefitinib monotherapy, clinical studies have demonstrated that combining gefitinib with external beam radiation to 66-74Gy and concurrent weekly chemotherapy after induction chemotherapy were tolerated without excessive toxicity. In the present trail, we hope to build on our own experience of using combined gefitinib and thoracic radiation with 3D-CRT or intensity-modulated radiotherapy (IMRT) technique in a phase I setting for stage IIIb and selected stage IV NSCLC. We will follow this treatment (RT and gefitinib) with 60 days gefitinib at standard systemic doses.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00497250
|Fudan University, Cancer Hospital, Department of Radiation Oncology|
|Shanghai, China, 200031|
|Principal Investigator:||Guoliang Jiang, MD||Fudan University Cancer Hospital, Department of Radiation Oncology|
|Principal Investigator:||Min Fan, M.D.||Fudan University Cancer Hospital, Department of Radiation Oncology|
|Principal Investigator:||Xiaolong Fu, M.D||Fudan University Cancer Hospital, Department of Radiation Oncology|