Combination Chemotherapy and Computer-Planned Radiation Therapy in Treating Patients With Unresectable Stage III Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Computer systems that allow doctors to create a 3-dimensional picture of the tumor to plan treatment may result in more effective radiation therapy. It is not yet known which chemotherapy and/or radiation therapy regimen is more effective in treating non-small cell lung cancer. PURPOSE: Randomized phase II trial to compare the effectiveness of different combination chemotherapy regimens and 3-dimensional radiation therapy in treating patients who have unresectable stage III non-small cell lung cancer.

Detailed Description
-----------------
OBJECTIVES: Compare the overall response rate, failure-free survival, and survival of patients with inoperable stage IIIA or IIIB non-small cell lung cancer treated with paclitaxel and carboplatin with concurrent 3-dimensional conformal radiotherapy (3-D XRT) vs gemcitabine and carboplatin with concurrent 3-D XRT. Compare the toxicity of these regimens in these patients. Compare the pattern of failure (locoregional vs distant failure) in patients treated with these regimens. Determine the feasibility of delivering 3-D XRT to patients in this multicenter study. OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms. Arm I: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patients then receive paclitaxel IV over 1 hour followed by carboplatin IV over 30 minutes once weekly and 3-dimensional conformal radiotherapy (3-D XRT) once daily 5 days a week. Treatment repeats weekly for 7 courses. Arm II: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patients then receive gemcitabine IV over 30 minutes twice weekly and 3-D XRT as in arm I. Treatment repeats weekly for 7 courses. In both arms, treatment continues in the absence of disease progression. Patients are followed every 2 months for 2 years, every 4 months for 2 years, and then annually for 2 years. PROJECTED ACCRUAL: A total of 82 patients (41 per treatment arm) will be accrued for this study within 9 months.

Official Title
-----------------
Induction/Concurrent Chemotherapy and Dose-Escalated Three Dimensional Thoracic Radiation for Patients With Stage III Non Small Cell Lung Cancer: A Randomized Phase II Study

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Drug: carboplatin
* Drug: gemcitabine hydrochloride
* Drug: paclitaxel
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) Squamous cell carcinoma Adenocarcinoma, including bronchoalveolar cell carcinoma Large cell anaplastic carcinoma, including giant and clear cell carcinoma Inoperable stage IIIA or IIIB disease No direct invasion of vertebral body Tumors adjacent to a vertebral body without bone invasion allowed if all gross disease can be encompassed in radiotherapy boost field Contralateral mediastinal disease (N3) allowed if all gross disease can be encompassed in radiotherapy boost field No scalene, supraclavicular, or contralateral hilar node involvement Transudate, cytologically negative, non-bloody pleural effusion allowed if it can be encompassed in radiotherapy field No exudative, bloody, or cytologically malignant pleural effusion Evidence of pleural effusion by chest CT scan but not chest x-ray that is too small to tap allowed At least 1 unidimensionally measurable lesion At least 20 mm by conventional techniques OR At least 10 mm by spiral CT scan The following are not considered measurable disease: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions Tumor lesions in a previously irradiated field PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin less than 1.5 mg/dL AST less than 2 times upper limit of normal Renal: Creatinine clearance 20-130 mL/min for females Creatinine clearance 20-150 mL/min for males Pulmonary: FEV1 at least 1.2 L Other: Not pregnant or nursing Fertile patients must use effective contraception No other currently active malignancy (defined as completed prior therapy and considered to be at less than 30% risk of relapse) except non-melanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for NSCLC No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy except steroids for adrenal failure or septic shock, hormones for non-disease-related conditions (e.g., insulin for diabetes), or glucocorticosteroids as antiemetics Radiotherapy: See Disease Characteristics No prior radiotherapy for NSCLC Surgery: At least 2 weeks since prior exploratory thoracotomy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paclitaxel + Carboplatin<br>Paclitaxel and carboplatin induction (2 cycles)followed by chemotherapy with the addition of radiotherapy for 7 cycles | Drug: carboplatin<br>* Arm A: AUC=6 IV over 30 min for 2 cycles then AUC=2 IV over 30 min q wk for 7 wks Arm B: AUC=5 IV over 30 min for 2 cycles<br>Drug: paclitaxel<br>* 225 mg/sq m IV over 3 hrs q 21 days for 2 cycles, then 45 mg/sq m IV over 1 hr q wk for 7 wks<br>Radiation: radiation therapy<br>* 3-D XRT 7400 cGy total after induction (during cycles 3-9)<br>|
| Experimental: Gemcitabine + Carboplatin<br>Gemcitabine and carboplatin induction (2cycles) followed by chemotherapy with the addition of radiotherapy for 7 cycles | Drug: carboplatin<br>* Arm A: AUC=6 IV over 30 min for 2 cycles then AUC=2 IV over 30 min q wk for 7 wks Arm B: AUC=5 IV over 30 min for 2 cycles<br>Drug: gemcitabine hydrochloride<br>* 1000 mg/sq m IV over 30 min days 1 & 8 repeat q 21 days for 2 cycles; then 35 mg/sq m IV over 30 min 2X wk for 7 wks<br>Radiation: radiation therapy<br>* 3-D XRT 7400 cGy total after induction (during cycles 3-9)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response | Response is assessed as failure free survival | 18 months post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 6 years post treatment | 
| Toxicity | Toxicity will be assessed during treatment | 13 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
squamous cell lung cancer, large cell lung cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer