Overview

This trial is active, not recruiting.

Conditions lung cancer, radiation toxicity
Treatments cetuximab, carboplatin, paclitaxel, 3-dimensional conformal radiation therapy
Phase phase 3
Target EGFR
Sponsor Radiation Therapy Oncology Group
Collaborator National Cancer Institute (NCI)
Start date November 2007
End date May 2016
Trial size 500 participants
Trial identifier NCT00533949, CALGB-30609, CDR0000564240, NCCTG-N0628, NCI-2013-01762, RTOG 0617

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Patients undergo standard-dose radiotherapy 5 days a week for 6 weeks. Patients receive concurrent chemotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Patients also receive consolidation treatment of paclitaxel and carboplatin. Treatment repeats in the absence of disease progression or unacceptable toxicity.
carboplatin
Given IV over 30 minutes
paclitaxel
Given IV over 1 hour (arm II closed to accrual effective 6/17/11)
3-dimensional conformal radiation therapy
Patients undergo radiation therapy 5 days a week (arm II closed to accrual effective 6/17/11)
(Experimental)
Patients undergo high-dose radiotherapy 5 days per week for 7.5 weeks. Patient also receive concurrent paclitaxel and carboplatin and receive consolidation treatment as in Arm I on days 1, 8, 15, 22, 29, 36 and 43. (closed to accrual effective 6/17/11)
carboplatin
Given IV over 30 minutes
paclitaxel
Given IV over 1 hour (arm II closed to accrual effective 6/17/11)
3-dimensional conformal radiation therapy
Patients undergo radiation therapy 5 days a week (arm II closed to accrual effective 6/17/11)
(Experimental)
Patients undergo standard-dose radiotherapy as in Arm I. Patients receive cetuximab and receive concurrent chemotherapy and consolidation treatment comprising cetuximab, paclitaxel, and carboplatin periodically for up to 16 weeks.
cetuximab
Given IV (arm IV closed to accrual effective 6/17/11)
(Experimental)
Patients undergo high-dose radiotherapy as in arm II and receive concurrent cetuximab, concurrent chemotherapy, and consolidation treatment as in Arm III. (closed to accrual effective 6/17/11)
cetuximab
Given IV (arm IV closed to accrual effective 6/17/11)

Primary Outcomes

Measure
Overall (Failure: death from any cause) survival
time frame: From randomization to date of death or last follow-up. Analysis occurs after 339 deaths have been reported.

Secondary Outcomes

Measure
Progression-free survival (Failure: occurrence of local or regional progression, distant metastases, or death from any cause)
time frame: From randomization to date of progression, death or last follow-up. Analysis occurs after 339 deaths have been reported.
Local-regional failure (Failure: occurrence of local or regional progression)
time frame: From randomization to date of local failure, death or last follow-up. Analysis occurs after 339 deaths have been reported.
Grade 3-5 esophagitis and pneumonitis adverse events as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0
time frame: From start of treatment to end of follow-up.
Other grade 3-5 adverse events as assessed by NCI CTCAE v3.0
time frame: From start of treatment to end of follow-up.
Death during or within 30 days of discontinuation of protocol treatment
time frame: From start of treatment to 24 months.
Quality of life (QOL) as measured by the Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) and lung cancer subscale (LCS)
time frame: From start of treatment to 24 months.
Patient-reported swallowing ability
time frame: From start of treatment to 24 months.
Quality-adjusted survival based on EuroQoL (EQ5D)-derived health utility score
time frame: From start of treatment to 24 months.
Correlation of tumor markers with overall survival, local-regional failure, and QOL
time frame: From randomization to date of failure (either local or regional), death or last follow-up. Analysis occurs after 339 deaths have been reported.
Prognostic and predictive effects of gross tumor volume on overall survival
time frame: From randomization to date of death or last follow-up. Analysis occurs after 339 deaths have been reported.
Prognostic value of pre-treatment standardized uptake value (SUV) of PET scan in predicting survival, distant metastasis, and local-regional control
time frame: From randomization to date of failure (either local or regional), death or last follow-up. Analysis occurs after 339 deaths have been reported.

Eligibility Criteria

Male or female participants at least 18 years old.

DISEASE CHARACTERISTICS: - Histologically or cytologically confirmed newly diagnosed non-small cell lung cancer (NSCLC) - Stage IIIA or IIIB disease - N3 supraclavicular disease or contralateral hilar lymph node involvement (i.e. greater than 1.5 cm on short axis or positive on PET scan) not allowed - N2 or N3 disease and an undetectable NSCLC primary tumor allowed - Unresectable or inoperable disease - No distant metastases - Pleural effusion allowed provided effusion is minimal and none of the following conditions are present: - Cytologically positive pleural effusion detectable by CT scan and chest x-ray (pleuracentesis required to confirm negative cytology of pleural fluid) - Greater than minimal pleural effusions (minimal effusions not detectable by chest x-ray and too small to tap safely are allowed) - Exudative pleural effusions, regardless of cytology - Malignant pleural effusion (T4 incurable disease) - Measurable or evaluable disease PATIENT CHARACTERISTICS: - Zubrod performance status 0-1 - Absolute neutrophil (ANC) ≥ 1,800 cells/mm³ - Platelet count ≥ 100,000 cells/mm³ - Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed) - Creatinine normal OR creatinine clearance ≥ 60 mL/min - Bilirubin normal - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal - Pulmonary Function Test (PFTs) including forced expiratory volume at 1 sec. (FEV1) ≥ 1.2 L/sec or ≥ 50% predicted (best value obtained prior to or after use of bronchodilator) - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective protection - No uncontrolled neuropathy ≥ grade 2 - Patients with post-obstructive pneumonia allowed - Patients must speak English or Spanish in order to complete the mandatory EORTC QLQ-30 and PRO-CTCAE, which are only available in certain languages - No prior invasive malignancy, except nonmelanoma skin cancer, carcinoma in situ of the breast, oral cavity, or cervix, unless the patient has been disease-free for the past 3 years - No prior severe infusion reaction to a monoclonal antibody - No weight loss of ≥ 10% within the past 4 weeks - No history of allergic reaction to paclitaxel or other taxanes, or to carboplatin - No severe, active comorbidity, including any of the following: - Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months - Transmural myocardial infarction within the past 6 months - Acute bacterial or fungal infection requiring IV antibiotics at the time of study entry - Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or within past 30 days precluding study therapy - Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects - AIDS - No significant history of uncontrolled cardiac disease, including any of the following: - Uncontrolled hypertension - unstable angina - Myocardial infarction within the past 6 months - Uncontrolled congestive heart failure - Cardiomyopathy with decreased ejection fraction PRIOR CONCURRENT THERAPY: - At least 3 weeks since prior exploratory thoracotomy (if performed) - Prior systemic chemotherapy allowed, provided it was not given for NSCLC - No prior therapy that specifically and directly targets the EGFR pathway - No prior radiotherapy to the region of NSCLC that would result in overlap of radiotherapy fields - No concurrent white blood cell (WBC) growth factors (i.e., filgrastim [G-CSF] or sargramostim [GM-CSF]) given during radiotherapy or prophylactically during consolidation chemotherapy

Additional Information

Official title 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
Principal investigator Jeffrey Bradley, MD
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 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), 4-dimensional CT planning utilization (yes vs no), 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) - Arm I: Patients undergo standard dose radiotherapy 5 days a week for 6 weeks for a total of 60 Gy. Patients receive concurrent chemotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Patients also receive consolidation treatment of paclitaxel and carboplatin on days 64 and 85. Treatment repeats in the absence of disease progression or unacceptable toxicity. - Arm II: Patients undergo high-dose radiotherapy 5 days per week for 7.5 weeks. Patient also receive concurrent paclitaxel and carboplatin as in Arm I on days 1, 8, 15, 22, 29, 36, and 43 . Patients also receive consolidation treatment comprising paclitaxel and carboplatin on days 71 and 92. (closed to accrual effective 6/17/11) - Arm III: Patients undergo standard-dose radiotherapy 5 days a week for 6 weeks for a total of 60 Gy. Patients receive cetuximab in addition to concurrent chemotherapy as in Arm I. Treatment continues with chemoradiation and cetuximab on days 8, 15, 22, 29, 36, and 43. Patients receive consolidation treatment of cetuximab on days 50, 57, 64, 71, 78, 85, 92, 99, and 106 and paclitaxel and carboplatin on days 71 and 92. - Arm IV: Patients undergo high-dose radiotherapy 5 days a week for 7.5 weeks for a total of 74 Gy. Patients receive cetuximab in addition to concurrent chemotherapy as in Arm I. Treatment continues with chemoradiation and cetuximab on days 8, 15, 22, 29, 36, 43, and 50. Patients receive consolidation treatment of cetuximab on days 57, 64, 71, 78, 85, 92, 99, 106, and 113 and paclitaxel and carboplatin on days 78 and 99. (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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Radiation Therapy Oncology Group.