Cisplatin, Vinorelbine, and Radiation Therapy in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cisplatin and vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether giving combination chemotherapy followed by radiation therapy is more effective than giving combination chemotherapy together with radiation therapy followed by more chemotherapy in treating non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying combination chemotherapy followed by radiation therapy to see how well it works compared to combination chemotherapy combined with radiation therapy followed by more chemotherapy in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Compare the overall survival of patients with stage III non-small cell cancer treated with chemotherapy comprising cisplatin and vinorelbine ditartrate (CV) followed by radical radiotherapy versus concurrent CV chemoradiotherapy followed by CV chemotherapy. Secondary Compare the progression-free survival of patients treated with these regimens. Compare the local progression-free survival (local control). Compare the hematological, pulmonary, esophageal, and neurological toxicities. Compare the response. Compare the quality of life. Compare the cost-effectiveness. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to clinically important factors. Patients are randomized to 1 of 2 treatment arms. Arm I (sequential treatment): Patients receive cisplatin IV over 2 hours on day 1 and vinorelbine ditartrate IV over 5-10 minutes on days 1 and 8. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning in week 15, patients undergo radiotherapy 5 days a week for 4 weeks. Arm II (concurrent treatment): Patients undergo radiotherapy as in arm I beginning in week 1. Patients receive cisplatin IV over 2 hours on days 1-4 and vinorelbine ditartrate IV over 5-10 minutes on days 1 and 8. Chemotherapy repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, monthly for 6 months, and then at each follow-up visit. After completion of study treatment, patients are followed periodically. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 508 patients will be accrued for this study.

Official Title
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A Randomized Phase III Trial of Sequential Chemotherapy Followed By Radical Radiotherapy Versus Concurrent Chemo-Radiotherapy Followed by Chemotherapy in Patients With Inoperable Stage III Non-Small Cell Lung Cancer and Good Performance Status

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Control arm (SEQ):
* Drug: Experimental arm (CON):


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed stage III non-small cell lung cancer (NSCLC) Patients with stage IIIB disease must not have a pleural effusion that is cytologically proven to be malignant Inoperable disease Disease must be able to be encompassed within a radical radiotherapy treatment volume PATIENT CHARACTERISTICS: ECOG performance status 0 or 1 Life expectancy > 3 months Patient considered able to tolerate platinum-based chemotherapy and radical radiotherapy Glomerular filtration rate ≥ 60 mL/min WBC > 3,000/mm³ Absolute neutrophil count > 1,500/mm³ Hemoglobin > 10.0 g/dL Patients with hemoglobin between 10 and 12 g/dL at randomization require a blood transfusion to ensure hemoglobin > 12 g/dL before starting radiotherapy Platelet count > 100,000/mm³ FEV_1 ≥ 1.0 L or DLCO (transfer factor) ≥ 50% of predicted Alkaline phosphatase ≤ 1.5 times upper limit of normal (ULN) Gamma-glutamyl-transferase < 1.5 times ULN Transaminases ≤ 1.5 times ULN Bilirubin ≤ 1.5 times ULN No medically unstable conditions (e.g., unstable diabetes, uncontrolled arterial hypertension, infection, hypercalcemia, or ischemic heart disease) Not pregnant or nursing Fertile patients must agree to use effective contraception Negative pregnancy test No other previous or current malignant disease likely to interfere with protocol treatment or comparisons PRIOR CONCURRENT THERAPY: No prior chemotherapy, radiotherapy, or investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sequential arm (SEQ)<br>Four cycles of cisplatinum/vinorelbine given in a 21 day cycle followed by radical radiotherapy, 55 Gy in 20 once daily fractions in four weeks (2.75 Gy/day). | Drug: Control arm (SEQ):<br>* Four cycles of cisplatinum/vinorelbine given in a 21 day cycle followed by radical radiotherapy, 55 Gy in 20 once daily fractions in four weeks (2.75 Gy/day).<br>|
| Experimental: Experimental arm (CON)<br>Concurrent chemo-radiotherapy [55 Gy in 20 daily fractions in 4 weeks (2.75 Gy/day) with cisplatinum given concurrently with fractions 1-4 and 16-19, and vinorelbine prior to fractions 1, 6, 15 and 20] followed by two cycles of cisplatinum/vinorelbine. | Drug: Experimental arm (CON):<br>* concurrent chemo-radiotherapy [55 Gy in 20 daily fractions in 4 weeks (2.75 Gy/day) with cisplatinum given concurrently with fractions 1-4 and 16-19, and vinorelbine prior to fractions 1, 6, 15 and 20] followed by two cycles of cisplatinum/vinorelbine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment related mortality (any cause) |  | from randomization till death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematological, pulmonary, esophageal, and neurological toxicities |  | From randomisation to the first 6 months | 
| Quality of life |  | at baseline, every 3 weeks for the first 6 months, then 3 monthly until 2 years, 6 monthly until 3 years, and annually thereafter | 
| Cost effectiveness |  | at baseline, every 3 weeks for the first 6 months, then 3 monthly until 2 years, 6 monthly until 3 years, and annually thereafter | 
| Overall survival and progression-free survival. |  | Overall Survival is the time between date of randomisation and date of death of any cause. Progression-free survival will be calculated from the date of randomisation to the date of first clinical evidence of progressive disease, or death. | 
| Local progression-free survival (local control) |  | From the date of randomisation to the date of first clinical evidence of progressive disease at the primary site, or death | 
| Response |  | proportion of patients in each treatment group whose best response in the first 6 months from randomisation is complete or partial will be reported. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer