NCT00533949

High-Dose or Standard-Dose Radiation Therapy and Chemotherapy With or Without Cetuximab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery

A Randomized Phase III Comparison of Standard-Dose (60 Gy) Versus High-Dose (74 Gy) Conformal Radiotherapy With Concurrent and Consolidation Carboplatin/Paclitaxel +/- Cetuximab (IND #103444) in Patients With Stage IIIA/IIIB Non-Small Cell Lung Cancer

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 544 (actual)
• Sponsor: Radiation Therapy Oncology Group · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel, carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether high-dose radiation therapy is more effective than standard-dose radiation therapy when given together with combination chemotherapy with or without cetuximab in treating patients with non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying high-dose or standard-dose radiation therapy given together with chemotherapy with or without cetuximab to see how well they work in treating patients with newly diagnosed stage III non-small cell lung cancer that cannot be removed by surgery.

Detailed description

OBJECTIVES: Primary * To compare the overall survival of patients with newly diagnosed, unresectable stage IIIA or IIIB non-small cell lung cancer treated with high- versus standard-dose conformal radiotherapy with concurrent and consolidation chemotherapy comprising carboplatin and paclitaxel. * To compare the overall survival of patients treated with versus without cetuximab in the setting of concurrent chemotherapy Secondary * To compare progression-free survival and local-regional tumor control in patients treated with these regimens. * To compare the toxicity of high- versus standard-dose conformal radiotherapy and concurrent chemotherapy with versus without cetuximab in these patients. * To investigate the prognostic and predictive effects of gross tumor volume on overall survival of patients treated with these regimens. * To compare the quality of life of patients treated with these regimens. * To correlate outcomes (i.e., survival, toxicity, or QOL) in these patients with biological parameters. * To analyze the predictive value of pre-treatment standardized uptake value (SUV) of positron emission tomography (PET) scan in predicting survival, distant metastasis, and local-regional control in patients treated with these regimens. * To explore biological markers to predict clinical outcome including survival, distant metastasis, local-regional control, and QOL (including toxicity) in patients treated with these regimens. * To prospectively collect and bank tissue, blood, and urine specimens for future biomarker analyses in predicting clinical outcome in patients treated with these regimens. * To investigate associations between epidermal growth factor receptor (EGFR) expression and toxicity, response, overall survival, and progression-free survival. OUTLINE: This is a multicenter study. Patients are stratified according to PET staging (yes vs no), radiotherapy technique (3-dimensional conformal radiotherapy vs intensity-modulated radiotherapy), Zubrod performance status (0 vs 1), and histology (squamous vs non-squamous). Patients are randomized to 1 of 4 treatment arms. (Arms II and IV closed to accrual effective 6/17/11) Patients may undergo tumor tissue, blood, and urine collection periodically during study for tissue banking or biomarker correlative studies. Patients may undergo quality-of-life assessment at baseline and periodically during study. After completion of study therapy, patients are followed periodically for 5 years and then annually thereafter.

Conditions

• Lung Cancer
• Radiation Toxicity

Interventions

Type	Name	Description
BIOLOGICAL	Cetuximab	Loading dose: 400 mg/m2, IV, one week prior to start of radiation therapy (RT). Then, beginning day 1 of RT, 250 mg/m2, IV, weekly; for 60 Gy arm for 15 weeks, for 74 Gy arm for 16 weeks.
DRUG	Carboplatin	Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy; for 74 Gy arms, on day 43 as well. Consolidation, 3 weeks after completion of RT, AUC=6, IV, days 1 and 22.
DRUG	Paclitaxel	Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy (RT); for 74 Gy arms, on day 43 as well. Consolidation, 3 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.
RADIATION	60 Gy RT	Radiation therapy (RT) in once-daily, 2 Gy fractions, given in 30 fractions over the course of 6 weeks.
RADIATION	74 Gy RT	Radiation therapy (RT) in once-daily, 2 Gy fractions, given in 37 fractions over the course of 7.5 weeks.

Timeline

• Start date: 2007-11-01
• Primary completion: 2013-06-01
• Completion: 2022-05-20
• First posted: 2007-09-24
• Last updated: 2022-06-21
• Results posted: 2017-05-05

Locations

213 sites across 2 countries: United States, Canada