Oxaliplatin, Docetaxel, and Radiation Therapy in Treating Patients With Unresectable Stage II/III or Recurrent NSCLC

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and docetaxel, 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. Oxaliplatin and docetaxel may make tumor cells more sensitive to radiation therapy. Giving oxaliplatin and docetaxel together with radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of oxaliplatin when given together with docetaxel and radiation therapy in treating patients with unresectable stage II or stage III or recurrent non-small cell lung cancer .

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of oxaliplatin when given with docetaxel and thoracic radiotherapy in patients with unresectable stage II, IIIA, or IIIB or recurrent non-small cell lung cancer. Secondary Determine the dose-limiting toxicities of this regimen in these patients. Determine the objective tumor response in patients treated with this regimen. OUTLINE: This is a dose-escalation study of oxaliplatin. Induction therapy: Patients undergo radiotherapy once a day on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47. Patients also receive docetaxel intravenous (IV) over 1 hour on days 1, 8, 15, 22, 29, 36, and 43 and oxaliplatin IV over 2-4 hours on days 2, 9, 16, 23, 30, 37, and 44. Patients with stable or responding disease proceed to consolidation therapy. Cohorts of 6 patients receive escalating doses of oxaliplatin during induction therapy until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose-limiting toxicity. Consolidation therapy: Beginning 3 weeks after the completion of induction therapy, patients receive consolidation therapy comprising docetaxel IV over 1 hour immediately followed by oxaliplatin IV over 2-4 hours on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 4 weeks and then every 3 months for up to 2 years.

Official Title
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Phase I Study of Oxaliplatin in Combination With Docetaxel and Radiotherapy in Patients With Unresectable or Recurrent Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: docetaxel
* Drug: oxaliplatin
* Procedure: radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of non-small cell lung cancer (NSCLC) meeting 1 of the following criteria: Medically inoperable or unresectable stage II, IIIA, or IIIB disease Post-resection intrathoracic tumor recurrence Measurable disease by computed tomography(CT) scan No evidence of small cell histology No significant pleural effusion on chest x-ray or malignant pleural effusion on cytology No metastatic disease Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1 Absolute granulocyte count ≥ 2,000/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 8.0 g/dL Bilirubin ≤ 1.5 mg/dL Serum glutamic oxaloacetic transaminase (SGOT) ≤ 1.5 times upper limit of normal (unless abnormality is caused by documented benign disease) Creatinine ≤ 1.5 mg/dL Weight loss ≤ 10% within the past 3 months Forced expiratory volume (FEV) 1 ≥ 1,000 cc Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study treatment Exclusion Criteria: Synchronous (except for nonmelanomatous skin cancer) or prior invasive malignancy, unless disease free for > 3 years Myocardial infarction within the past 6 months Symptomatic heart disease, including any of the following: Angina Congestive heart failure Uncontrolled arrhythmia Active infection or fever ≥ 38.5°C within the past 3 days Known hypersensitivity to any of the components of oxaliplatin or docetaxel Prior thoracic or neck radiotherapy Prior docetaxel or oxaliplatin

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemoradiation Treated Patients<br>Patients receiving Docetaxel, Oxaliplatin and radiotherapy. | Drug: docetaxel<br>* 60 mg/m2 on day 1 of each week during radiation therapy<br>* Other names: Taxotere;Drug: oxaliplatin<br>* Escalating dose per assignment: 20-50 mg/m2 on day 2 of each week during radiation therapy<br>* Other names: Eloxatin;Procedure: radiation therapy<br>* 2 Gy Days 1-5 each week, total dose of 70Gy<br>* Other names: radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of oxaliplatin in combination with docetaxel and radiotherapy |  | Within 90 days of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicities |  | Within 90 days of radiotherapy | 
| Objective tumor response |  | Every 3 months up to 24 months | 

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