Radiation Therapy Plus Chemotherapy in Treating Patients With 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. Combining more than one drug and combining chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: Randomized phase III trial to compare the effectiveness of various schedules of radiation therapy and combination chemotherapy using vinblastine and cisplatin or cisplatin and etoposide in treating patients with stage II or stage III non-small cell lung cancer that cannot be removed surgically.

Detailed Description
-----------------
OBJECTIVES: I. Compare the survival rate of patients with locally advanced, unresectable non-small cell lung cancer randomized to concomitant vinblastine/cisplatin (VBL/CDDP) and thoracic radiotherapy versus sequential VBL/CDDP and once-daily thoracic radiotherapy. II. Compare the survival rate of such patients randomized to 2 courses of concomitant etoposide/cisplatin and hyperfractionated thoracic radiotherapy versus sequential VBL/CDDP and once-daily thoracic radiotherapy. III. Assess the frequency of treatment-related esophageal and hematologic toxicity/morbidity in patients on concomitant versus sequential chemoradiation treatment arms. OUTLINE: Randomized study. The following acronyms are used: CDDP Cisplatin, NSC-119875 VBL Vinblastine, NSC-49842 VP-16 Etoposide, NSC-141540 Arm I: 2-Drug Combination Chemotherapy Followed by Radiotherapy. CDDP/VBL; followed by thoracic irradiation using photons of at least 6 MV (electrons may be used to boost the supraclavicular lymph nodes). Arm II: Radiotherapy plus 2-Drug Combination Chemotherapy. Thoracic irradiation using equipment as in Arm I; plus CDDP/VBL. Arm III: Hyperfractionated Radiotherapy plus 2-Drug Combination Chemotherapy. Thoracic irradiation using equipment as in Arm I; plus CDDP/VP-16. PROJECTED ACCRUAL: A total of 597 patients will be entered over 3.1-4.2 years. If fewer than 6 patients/month are accrued, the feasibility of the study will be re-evaluated.

Official Title
-----------------
A Three-Arm Phase III Study of Concomitant Versus Sequential Chemotherapy and Thoracic Radiotherapy for Patients With Locally Advanced Inoperable Non-small Cell Lung Cancer

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

Intervention / Treatment
-----------------
* Drug: cisplatin
* Drug: Etoposide
* Drug: Vinblastine
* Radiation: Radiation therapy
* Drug: Cisplatin
* Radiation: Radiation therapy
* Radiation: Radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Locoregionally advanced, inoperable, non-small cell lung cancer with no evidence of distant metastases, i.e.: Stage II/IIIA medically inoperable disease Stage IIIA/IIIB unresectable disease No pleural effusion Appearance after an invasive thoracic procedure allowed No more than 5% weight loss within 3 months prior to diagnosis Confirmed N2 disease should first be evaluated for protocol RTOG-9309 PATIENT CHARACTERISTICS: Age: At least 18 Performance status: Karnofsky 70%-100% Hematopoietic: AGC at least 2,000 Platelets at least 100,000 Hemoglobin at least 8.0 g/dL Hepatic: (unless abnormality caused by benign disease) Bilirubin no more than 1.5 times normal AST no more than 1.5 times normal Renal: Creatinine no more than 1.5 mg/dL Cardiovascular: No myocardial infarction within the past 6 months No angina No congestive heart failure No uncontrolled arrhythmia Other: No synchronous or prior invasive malignancy within 3 years except nonmelanomatous skin cancer No pregnant women Effective contraception required of fertile patients PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior thoracic or neck radiotherapy Surgery: No prior complete or nearly complete tumor resection

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 |
| --- | --- |
| Active Comparator: Arm 1: Sequential ChemoRT<br>Vinblastine 6 mg/m2 i.v. bolus weekly first 5 weeks Cisplatin 100 mg/m2 i.v. over 30-60 minutes, days 1 & 29 RT: 63 Gy/7 wks/34 daily fractions (1.8 Gy X 25 fx then 2.0 Gy X 9 fx) beginning day 50 | Drug: cisplatin<br>* 100 mg/m2 i.v. over 30-60 minutes, days 1 & 29<br>Drug: Vinblastine<br>* 5 mg/m2 i.v. bolus weekly first 5 weeks of RT<br>Radiation: Radiation therapy<br>* 63 Gy/7 wks/34 daily fractions (1.8 Gy X 25 fx then 2.0 Gy X 9 fX) beginning day 50 of protocol treatment<br>|
| Experimental: Arm 2: Concurrent STD RT<br>Vinblastine 5 mg/m2 i.v. bolus weekly first 5 weeks Cisplatin 100 mg/m2 i.v. over 30-60 minutes, days 1 & 29 RT: 63 GY/7 wks/34 daily fractions (1.8 Gy X 25 fx then 2.0 Gy X 9 fx) beginning day 1 | Drug: cisplatin<br>* 100 mg/m2 i.v. over 30-60 minutes, days 1 & 29<br>Drug: Vinblastine<br>* 5 mg/m2 i.v. bolus weekly first 5 weeks of RT<br>Radiation: Radiation therapy<br>* 63 Gy/7 wks/34 daily fractions (1.8 Gy X 25 fx then 2.0 Gy X 9 fx) beginning day 1 of protocol treatment<br>|
| Experimental: Arm 3: Concurrent HFX RT<br>Oral VP-16 50 mg b.i.d. X 10 only on RT treatment days 1-5, 8-12, 29-33, and 36-40 (76 mg/day if BSA < 1.7m2) Cisplatin 50 mg/m2 i.v. over 30-60 minutes on days 1, 8, 29, and 36 RT: 69.6 Gy/6 wks/58 X 1.2 Gy twice daily fractions (at least 6 hours apart) beginning day 1 | Drug: Etoposide<br>* Oral etoposide given 50 mg b.i.d. X 10 only on RT treatment days 1-5, 8-12, 29-33, and 36-40. 75 mg/day if body surface area < 1.7 m2<br>* Other names: VP-16;Drug: Cisplatin<br>* 50 mg/m2 i.v. over 30-60 minutes on days 1, 8, 29, and 36<br>Radiation: Radiation therapy<br>* 69.6 Gy/6 wks/58 X 1.2 Gy twice daily fractions (at least 6 hours apart) beginning day 1 of protocol therapy<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | from date of randomization to date of death or last follow-up for patients still alive | 

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