Pulmonart: Docetaxel - Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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Primary Objective: To evaluate the toxicity/safety profile of docetaxel/cisplatin induction therapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy followed by consolidation docetaxel/cisplatin in patients with locally advanced unresectable NSCLC (stage IIIA- multiple cN2 or IIIB). Secondary Objective: To estimate efficacy parameters in overall response rate, progression free survival and 1 year survival for each of the two above mentioned arms.

Official Title
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A Two Arm Phase II Study Comparing Docetaxel/Cisplatin Induction Therapy Followed By Concurrent Chemoradiotherapy Versus Concurrent Chemoradiotherapy Followed By Consolidation Docetaxel/Cisplatin in Patients With Locally Advanced Unresectable NSCLC (Stage IIIA-Multiple cN2 or IIIB)

Conditions
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Lung Neoplasms

Intervention / Treatment
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* Drug: docetaxel and cisplatin followed by concurrent chemoradiotherapy with docetaxel and cisplatin + radiotherapy
* Drug: docetaxel and cisplatin + radiotherapy followed by docetaxel and cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically or cytologically confirmed NSCLC (adenocarcinoma, squamous cell carcinoma, large cell carcinoma or a combination of these) Patients must have a locoregionally advanced unresectable NSCLC Stage IIIA with multiple level clinical N2 nodes (preferably with histological or cytological confirmation). Patients with peripheral tumours of the lower lobe with contralateral upper mediastinal nodes at station N2 are excluded Stage IIIB T4 or N3 In the T4 category, patients with pleural or pericardial effusion and multiple nodules in the same lobe are excluded. Patients with T4 disease secondary to extensive and massive involvement of the great vessels are excluded. Patients should be excluded when the expected risk of pulmonary toxicity is likely to be high, e.g. V20 in excess of 35%. Life expectancy of at least 12 weeks. WHO performance status 0 or 1. Weight loss ≤ 10% within the last 3 months. Laboratory requirements at entry (within 7 days before randomization): Blood cell counts: Absolute neutrophils ≥ 2.0 x 10^9/L Platelets ≥ 100 x 10^9/L Hemoglobin ≥ 10 g/dl Renal function: _Serum creatinine ≤1 x the upper limit of normal (UNL). In case of borderline value of serum creatinine, the 24h creatinine clearance should be ≥ 60 mL/min Hepatic functions: Serum bilirubin ≤ 1 x UNL ASAT and ALAT ≤ 2.5 x UNL Alkaline phosphatase ≤ 5 x UNL. Patients with ASAT and/or ALAT > 1.5 x UNL associated with alkaline phosphatase > 2.5 x UNL are not eligible for the study. Lung function tests at entry: FEV1: ≥ 50 % x Normal value DLco: ≥ 50 % x Normal value. Adequate cardiac function. Patient with either measurable and/or non-measurable lesion (according to RECIST criteria). Exclusion criteria: Diagnosis of small cell lung cancer Pregnant or lactating women Patients (male or female) with reproductive potential not implementing adequate contraceptive measures Prior systemic chemotherapy, immunotherapy, or biological therapy including neoadjuvant or adjuvant treatment for NSCLC Prior surgery for NSCLC, if less than 5 years from study Prior radiotherapy for NSCLC History of prior malignancies, except for cured non-melanoma skin cancer, curatively treated in situ carcinoma of the cervix or other cancer curatively treated and with no evidence of disease for at least five years. Symptomatic peripheral neuropathy Grade ≥ 2 except if due to trauma. Other serious concomitant illness of medical conditions: Congestive heart failure or angina pectoris except if it is medically controlled. Previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or arrhythmias. History of significant neurologic or psychiatric disorders including dementia or seizures. Active infection requiring IV antibiotics. Active ulcer, unstable diabetes mellitus or other contra-indication to corticosteroid therapy. Superior vena cava syndrome contra-indicating hydration. Preexisting pericardial effusion. Preexisting symptomatic pleural effusion. Significant gastrointestinal abnormalities, including requirement for intravenous nutrition, active peptic ulcer disease, prior surgical procedures affecting absorption. Distant metastasis. Concurrent treatment with any other experimental anti-cancer drugs. Concomitant or within 4-week period administration of any other experimental drug under investigation. Significant ophthalmologic abnormalities. Moderate to severe dermatitis. Hypersensitivity to docetaxel or any of its excipients. Concomitant use of phenytoin, carbamazepin, barbiturates, or rifampicin. Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study. Patient unlikely to comply with protocol, i.e., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Experimental: B<br>Concurrent chemoradiotherapy followed by consolidation chemotherapy | Drug: docetaxel and cisplatin + radiotherapy followed by docetaxel and cisplatin<br>* docetaxel (20mg/m2, IV) and cisplatin (20 mg/m2) weekly for 6 weeks + radiotherapy 2 Gy/day, 5 days per week to a total dose of 66 Gy followed by docetaxel and cisplatin (40 mg/m2, IV, Day 1, 2) every 3 weeks for 2 cycles.<br>|
| Experimental: A<br>Induction chemotherapy followed by concurrent chemoradiotherapy | Drug: docetaxel and cisplatin followed by concurrent chemoradiotherapy with docetaxel and cisplatin + radiotherapy<br>* docetaxel (75mg/m2, IV, Day 1) and cisplatin (40 mg/m2, IV, Day 1, 2) every 3 weeks for 2 cycles, followed by concurrent chemoradiotherapy with docetaxel (20 mg/m2, IV) and cisplatin (20 mg/m2) weekly for 6 weeks + radiotherapy 2 Gy/day, 5 days per week to a total dose of 66 Gy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| anti-tumor activity including overall response rate |  | assessed at the end of the full course of treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| all treatment related acute and chronic toxicity assessed according to the NCI-CTC scale |  | throughout the study | 
| other adverse events not reported in the NCI-CTI scale |  | throughout the study | 
| hematological and non-hematological toxicities |  | reported for all grades observed during each cycle |