Ph II Concurrent Chemo t/Docetaxel/Carboplatin/Radio Therapy-consolidation t/Locally Adv Inoperable Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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RATIONALE: Because of its success in advanced NSCLC both as a single agent and in combination with other chemotherapeutics, it is reasonable to investigate the efficacy and toxicity of docetaxel as a multimodality regimen in this patient population. Docetaxel at a dose of 20 mg/m2 appears to be a well-tolerated weekly dose when combined with either cisplatin 25 mg/m2 20-22 or carboplatin area under the curve (AUC) 2 23-25 concomitant with radiation therapy. PURPOSE: To explore the potential benefits of the radiosensitizing effects of weekly docetaxel/carboplatin/radio therapy concurrent therapy followed full dose systemic docetaxel/carboplatin consolidation therapy on overall response rate, survival, progression-free survival, safety and toxicity in patients with locally advanced NSCLC.

Detailed Description
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OBJECTIVES: Primary To determine the overall survival (0S) for advanced NSCLC patients receiving concurrent chemoradiotherapy with weekly docetaxel, carboplatin and radiation therapy followed by two cycles of consolidation chemotherapy with docetaxel and carboplatin. Secondary To determine the overall response rate in patients treated with this regimen. To determine the time to disease progression in patients treated with this regimen. To assess the safety and tolerability of this regimen in these patients. OUTLINE: This is a Phase II, open label, multi-center study to determine the overall survival rate for patients treated with concurrent chemoradiotherapy with weekly docetaxel, carboplatin and radiation followed by two cycles of consolidation chemotherapy with docetaxel and carboplatin. Eligible patients will receive concurrent therapy with docetaxel (20 mg/m2) administered weekly for seven weeks as a 30-minute intra-venous (IV) infusion followed by carboplatin (AUC 2) administered weekly for seven weeks as a 30-minute IV infusion. Concurrent radiation therapy will be administered at a dose of 1.8 Gy daily 5 days/week for 25 fractions followed by a dose of 2.0 Gy daily, 5 days/week for 9 fractions (total of 34 fractions). There will be a three-week rest period following the end of the concurrent chemotherapy after which the consolidation phase will begin. During this phase of the study, patients will be treated with docetaxel (75 mg/m2) administered as a 1-hour IV infusion followed by carboplatin (AUC 6) administered as a 30-minute IV infusion. Patient will be treated every three weeks for a total of two cycles.

Official Title
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PhII Study of Concurrent Chemoradiotherapy With Weekly Docetaxel, Carboplatin and Radiation Therapy Followed by Consolidation Chemotherapy With Docetaxel and Carboplatin for Locally Advanced Inoperable Non-small Cell Lung Cancer (NSCLC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Docetaxel
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must voluntarily sign and date an informed consent before the initiation of any study procedures Patients must have non-metastatic, inoperable, Stage IIIA or IIIB histologically or cytologically documented NSCLC without evidence of malignant pleural effusion Patients must not have received any prior systemic chemotherapy, thoracic radiotherapy or surgical resection for treatment of NSCLC Patients must have at least one site of unidirectionally measurable disease Patients must be ≥ 3 weeks from a formal exploratory thoracotomy Patients must have a Radiation Oncology and Medical Oncology consult and approval prior to study entry Patients must be ≥ 18 years of age Women of childbearing potential must have a negative baseline serum pregnancy within 7 days prior to Week 1, Day 1 and must not be breast feeding. Women of childbearing potential and men with a sexual partner of child bearing potential must use an effective method of contraception beginning prior to study entry, for the duration of the study participation and for a minimum of 3 months after the last dose of chemotherapy. Patients must have adequate hepatic, renal, lung and bone marrow function as defined below: Absolute neutrophil count (ANC) > 1,500/mm3 Hemoglobin > 9.0 gm/dL Creatinine < 1.5 Platelets > 100,000/mm3 Total bilirubin within normal limits (WNL) AST or ALT and Alkaline Phosphatase must be within the range allowing for eligibility, as per chart on page 10 of the protocol. Calculated CrCl > 50 ml/min (via Cockroft-Gault formula). Forced expiratory volume in 1 second (FEV 1) > 800 ml Exclusion Criteria: Known hypersensitivity to drugs formulated with polysorbate 80 Peripheral neuropathy Grade ≥ 2. Wet stage IIIB (documented malignant pleural effusion) or stage IV NSCLC Previous chemotherapy or radiation therapy Any concomitant malignancy, brain metastasis or uncontrolled, clinically significant medical or psychiatric disorder Pregnant or nursing women A greater than or equal to 10% weight loss over the past 3 months

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Therapeutic Intervention<br> | Drug: Carboplatin<br>* Carboplatin will be given weekly for seven weeks beginning on Day 1 of the study as a 30-minute intravenous infusion during concurrent therapy. Carboplatin will be given once every three weeks as a 30-minute intravenous infusion immediately following the infusion of docetaxel. Patients will receive two cycles of consolidation treatment.<br>* Other names: None specified;Drug: Docetaxel<br>* Docetaxel will be given weekly for seven weeks beginning on Day 1 of the study as a 30-minute intravenous infusion during concurrent therapy. Docetaxel will be given once every three weeks administered as a one-hour IV infusion. Patients will receive two cycles of consolidation treatment (1 cycle = 3 weeks).<br>* Other names: Taxotere;Radiation: radiation therapy<br>* Radiotherapy will be administered daily X 5 day/week for 34 days beginning on Day 1 of the study. Radiotherapy will follow immediately after the infusions of docetaxel and carboplatin.<br>* Other names: none specified;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Months from on-study to expired/last date known alive. | 14.95 months (average duration, on study date to off-study date) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Patient response to treatment per RECIST: Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started Complete response (CR): disappearance of all target lesions Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD | on-study date to date of best response | 
| Time to Disease Progression | Time to disease progression in months | on-study date to date of progression | 
| Number of Participants With Adverse Events by Grade | Number of participants with adverse events, according to grade of event, using the NCI Common Toxicity Criteria (version 2.0) grading system to assign a grade to each event with 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, and 5 = death related to adverse event | 30 days after last treatment. | 

 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