ZD1839 (NSC #715055, IND #61187) With Induction Paclitaxel And Carboplatin Followed By Either Radiation Or Concomitant Radiation With Weekly Paclitaxel And Carboplatin In Stage III Non-Small Cell Lung Cancer, A Phase II Study
Overview
- Phase
- Phase 2
- Intervention
- gefitinib
- Conditions
- Adenocarcinoma of the Lung
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 144
- Locations
- 1
- Primary Endpoint
- Overall survival (Stratum I)
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
This phase II clinical trial studies how well combining different regimens of chemotherapy and gefitinib with radiation therapy work in treating patients with stage III non-small cell lung cancer. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies such as gefitinib may interfere with the growth of tumor cells and slow the growth of non-small cell lung cancer. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving different regimens of combination therapy together with gefitinib and radiation therapy may be an effective treatment for non-small cell lung cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To determine whether ZD1839 (gefitinib) at 250 mg orally every day administered concomitantly with radiotherapy after induction treatment consisting of paclitaxel, carboplatin, and ZD1839 among patients with inoperable stage III non-small cell lung cancer and Common Terminology Criteria (CTC) performance status 2 or poor risk performance status 0-1 is tolerable. II. To determine whether ZD1839 at 250 mg orally every day administered concomitantly with paclitaxel, carboplatin, and radiation after induction treatment consisting of paclitaxel, carboplatin, and ZD1839 among patients with inoperable stage III non-small cell lung cancer and CTC performance status 0-1 is tolerable. III. To determine the overall response rate, failure-free survival, and survival after treatment with induction chemotherapy with daily ZD1839, concomitant radiotherapy and daily ZD1839, and post-radiotherapy single agent daily ZD1839 among patients with CTC performance status 2 or poor risk performance status 0-1 and inoperable stage III non-small cell lung cancer. IV. To determine the overall response rate, failure-free survival, and survival after treatment with induction chemotherapy and daily ZD1839, concomitant chemoradiotherapy and daily ZD1839, and post-radiotherapy single agent daily ZD1839 among patients with CTC performance status 0-1 and inoperable stage III non-small cell lung cancer. V. To determine if elevated circulating epidermal growth factor receptor (EGFR) levels prior to treatment, as determined by either quantitative polymerase chain reaction (PCR) or direct enzyme-linked immunosorbent assay (ELISA) measurement, may predict for response to therapy with EGFR inhibitors. OUTLINE: All patients receive induction therapy comprising paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patients then receive therapy based on their assigned stratum. STRATUM I: Patients receive gefitinib orally (PO) daily for 7 weeks. Patients also undergo concurrent radiotherapy once daily 5 days a week for 7 weeks. STRATUM II: Patients receive gefitinib and radiotherapy as in stratum I concurrently with paclitaxel IV over 1 hour followed by carboplatin over 30 minutes once weekly for 7 weeks. Patients then receive gefitinib PO daily in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically documented non-small cell lung cancer (NSCLC), including squamous cell carcinoma, adenocarcinoma (including bronchoalveolar cell), and large cell anaplastic carcinoma (including giant and clear cell carcinomas)
- •ELIGIBLE DISEASE STAGES: Inoperable IIIA and selected IIIB
- •Generally, patients entered must be considered unresectable or inoperable; patients with T1 or T2, N2 disease are eligible; patients with T3, N2 or T4, N0-N2 disease are eligible if based on the closeness to the carina, invasion of the mediastinum or invasion of the chest wall; patients with T3, N0-N1 disease are not eligible; patients must be M0 (M1 patients are not eligible)
- •Patients with direct invasion of vertebral body are ineligible
- •Patients with tumors adjacent to a vertebral body are eligible, unless there is demonstrable bone invasion, as long as all gross disease can be encompassed in the radiation boost field in accordance with the homogeneity criteria
- •Patients with contralateral mediastinal disease (N3) are eligible if all gross disease can be encompassed in the radiation boost field in accordance with the homogeneity criteria; patients with scalene, supraclavicular, or contralateral hilar node involvement are ineligible
- •Patients with a pleural effusion, which is a transudate, cytologically negative and non-bloody, are eligible if the radiation oncologist feels the tumor can be encompassed within a reasonable field of radiotherapy. Patients with exudative, bloody, or cytologically malignant effusions are not eligible; if a pleural effusion can be seen on the chest computed tomography (CT) but not on chest x-ray (CXR) and is too small to tap, the patient will be eligible; a pleural effusion appearing only after a thoracotomy or other invasive thoracic procedure was attempted will not make a patient ineligible
- •PATIENTS MUST HAVE MEASURABLE DISEASE
- •Lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as ≥10 mm with spiral CT scan
- •Lesions that are not considered measurable include the following:
Exclusion Criteria
- Not provided
Arms & Interventions
Stratum I (gefitinib, radiotherapy)
Patients receive gefitinib orally (PO) daily for 7 weeks. Patients also undergo concurrent radiotherapy once daily 5 days a week for 7 weeks. Patients then receive gefitinib PO daily in the absence of disease progression or unacceptable toxicity.
Intervention: gefitinib
Stratum I (gefitinib, radiotherapy)
Patients receive gefitinib orally (PO) daily for 7 weeks. Patients also undergo concurrent radiotherapy once daily 5 days a week for 7 weeks. Patients then receive gefitinib PO daily in the absence of disease progression or unacceptable toxicity.
Intervention: radiation therapy
Stratum I (gefitinib, radiotherapy)
Patients receive gefitinib orally (PO) daily for 7 weeks. Patients also undergo concurrent radiotherapy once daily 5 days a week for 7 weeks. Patients then receive gefitinib PO daily in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis
Stratum II (gefitinib, radiotherapy, chemotherapy)
Patients receive gefitinib and radiotherapy as in stratum I concurrently with paclitaxel IV over 1 hour followed by carboplatin over 30 minutes once weekly for 7 weeks. Patients then receive gefitinib PO daily in the absence of disease progression or unacceptable toxicity.
Intervention: paclitaxel
Stratum II (gefitinib, radiotherapy, chemotherapy)
Patients receive gefitinib and radiotherapy as in stratum I concurrently with paclitaxel IV over 1 hour followed by carboplatin over 30 minutes once weekly for 7 weeks. Patients then receive gefitinib PO daily in the absence of disease progression or unacceptable toxicity.
Intervention: carboplatin
Stratum II (gefitinib, radiotherapy, chemotherapy)
Patients receive gefitinib and radiotherapy as in stratum I concurrently with paclitaxel IV over 1 hour followed by carboplatin over 30 minutes once weekly for 7 weeks. Patients then receive gefitinib PO daily in the absence of disease progression or unacceptable toxicity.
Intervention: gefitinib
Stratum II (gefitinib, radiotherapy, chemotherapy)
Patients receive gefitinib and radiotherapy as in stratum I concurrently with paclitaxel IV over 1 hour followed by carboplatin over 30 minutes once weekly for 7 weeks. Patients then receive gefitinib PO daily in the absence of disease progression or unacceptable toxicity.
Intervention: radiation therapy
Stratum II (gefitinib, radiotherapy, chemotherapy)
Patients receive gefitinib and radiotherapy as in stratum I concurrently with paclitaxel IV over 1 hour followed by carboplatin over 30 minutes once weekly for 7 weeks. Patients then receive gefitinib PO daily in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Overall survival (Stratum I)
Time Frame: From randomization until death or last known follow-up, assessed up to 13 months
Kaplan-Meier curves will be used to describe overall survival in each stratum.
Response to induction treatment
Time Frame: Up to 3 years
Summarized by treatment group. Exact binomial confidence intervals will be computed for these response rates.
Overall survival (Stratum II)
Time Frame: From randomization until death or last known follow-up, assessed up to 14.5 months
Kaplan-Meier curves will be used to describe overall survival in each stratum.
Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time Frame: Up to 3 years
The frequency of toxicity occurrence will be tabulated by the most severe occurrence.
Overall response
Time Frame: Up to 3 years
Overall response to the full treatment regimen will be summarized by treatment group. Exact binomial confidence intervals will be computed for these response rates.
Failure-free survival
Time Frame: Time between randomization and disease progression, death, or last known follow-up, assessed up to 3 years
Kaplan-Meier curves will be used to describe failure-free survival in each stratum. Within each treatment group, the pattern of treatment failure (local, distant, regional) will be summarized.