Concurrent Once Daily Versus Twice Daily Radiotherapy for Limited Stage Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as cisplatin and etoposide, 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. It is not yet known which schedule of radiation therapy is more effective when given together with chemotherapy in treating small cell lung cancer. PURPOSE: This randomized phase III trial is studying two different schedules of radiation therapy to compare how well they work when given together with cisplatin and etoposide in treating patients with limited stage small cell lung cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Compare overall survival of patients with limited stage small cell lung cancer treated with chemoradiotherapy comprising cisplatin, etoposide, and once vs twice daily radiotherapy. Secondary Compare local progression-free survival of patients treated with these regimens. Compare metastasis-free survival of patients treated with these regimens. Compare the toxicity of these regimens in these patients. Compare response rates in patients treated with these regimens. Compare the cytotoxic dose intensity of these regimens in these patients. Compare the dose intensity of two different schedules of radiotherapy in these patients. OUTLINE: This is a multicenter, randomized, controlled study. Patients are stratified according to participating center, ECOG performance status (0-1 vs 2), and lactic dehydrogenase, sodium, and alkaline phosphatase levels. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive cisplatin IV over 2 hours on days 1-3 OR on day 1 only and etoposide IV over 45-90 minutes on days 1-3. Treatment repeats every 21 days for up to 6 courses. During course 2, patients undergo concurrent radiotherapy once daily 5 days a week for 6½ weeks (total of 33 fractions). Arm II: Patients receive cisplatin and etoposide as in arm I. During courses 2 and 3, patients undergo concurrent radiotherapy twice daily 5 days a week for 3 weeks (total of 30 fractions). In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 3-4 weeks after completion of chemoradiotherapy, patients in both arms achieving a complete or partial response with no evidence of brain metastasis undergo prophylactic cranial irradiation once daily 5 days a week for 2 weeks (total of 10 fractions). After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 532 patients will be accrued for this study.

Official Title
-----------------
A 2-Arm Randomized Controlled Trial of Concurrent Chemo-Radiotherapy Comparing Twice-Daily and Once-Daily Radiotherapy Schedules in Patients With Limited Stage Small Cell Lung Cancer (SCLC) and Good Performance Status [CONVERT]

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

Intervention / Treatment
-----------------
* Radiation: Once daily radiotherapy
* Radiation: Twice daily radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion/exclusion criteria: Either sex, age ≥18 years Performance status ECOG grade 0-1. Patients with PS 2 whose general condition is explained by obstructive/bulky disease likely to improve after the first cycle of chemotherapy can be included at the discretion of the local investigator. Patients with PS 2 as a result of comorbid conditions will be excluded. Histologically or cytologically confirmed SCLC No patients with mixed small-cell and non-small-cell histologic features No history of previous malignancy in the last 5 years (except non melanomatous skin or in-situ cervix carcinoma). Patients with previous malignancies (except breast cancer) and in remission for at least 5 years can be included. Limited stage disease (Veterans Administration Lung Cancer Study Group) ie patients whose disease can be encompassed within a radical radiation portal. No pleural or pericardial effusions proven to be malignant RT target volume acceptable by the local radiotherapist Pulmonary function FEV1 >1 litre or 40% predicted value KCO (DLCO/VA) >40%predicted Maximum of one of the following adverse biochemical factors: Serum alkaline phosphatase more than >1.5 times the upper limit of normal (ULN) Serum sodium < Lower limit of Normal Serum LDH > ULN Normal serum creatinine and calculated creatinine clearance >50 ml/min. If calculated creatinine clearance is <50 ml/mn according to the Cockroft and Gault formula, an EDTA clearance should be performed Adequate haematological function Neutrophils >1.5 x 109/l Platelets >100 x 109/l Adequate liver function: ALT & AST <= 2.5 x ULN No other previous or concomitant illness or treatment which in the opinion of the clinician will interfere with the trial treatments or comparisons No prior surgical resection of the primary tumour, no prior radiotherapy for lung cancer Considered fit to receive any of the trial regimens Female patients must satisfy the investigator that they are not pregnant, or are not of child-bearing potential, or are using adequate contraception. Men must also use adequate contraception, as etoposide is clastogenic. Patients must not be breastfeeding Patient has read the patient information sheet and has signed the consent form. Patients available for follow-up

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: Once daily radiotherapy<br>Once daily radiotherapy | Radiation: Once daily radiotherapy<br>* Standard of care chemotherapy (cisplatin/etoposide) + once daily radiotherapy<br>Radiation: Twice daily radiotherapy<br>* Standard of care chemotherapy (cisplatin/etoposide) + twice daily radiotherapy<br>|
| Active Comparator: Twice daily radiotherapy<br>Twice daily radiotherapy | Radiation: Once daily radiotherapy<br>* Standard of care chemotherapy (cisplatin/etoposide) + once daily radiotherapy<br>Radiation: Twice daily radiotherapy<br>* Standard of care chemotherapy (cisplatin/etoposide) + twice daily radiotherapy<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | August 2015 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local progression-free survival |  | August 2015 | 
| Metastasis-free survival |  | August 2015 | 
| Toxicity of treatment |  | August 2015 | 
| Cytotoxic dose intensity |  | August 2015 | 
| Radiotherapy dose intensity |  | August 2015 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
limited stage small cell lung cancer