Phase 2 Study Evaluating Mid-position Strategy in Radiotherapy Treatment for Patients With a Locally Advanced Non-small Cell Lung Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to establish on the market and to clinically evaluate a new strategy of treatment for patients with locally advanced non-small cell lung cancer using deformable repositioning of 4D imaging.

Official Title
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Randomized Phase 2 Study Evaluating the Interest of Mid-position Strategy Versus ITV (Internal Target Volume) Strategy in Radiotherapy Treatment for Patients With a Locally Advanced Non-resected Non-small Cell Lung Carcinoma (NSCLC).

Conditions
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Non-small Cell Lung Cancer, Radiation Therapy, Locally Advanced Disease, Non-metastatic Disease, Non-resectable Disease

Intervention / Treatment
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* Radiation: mid-position radiation strategy
* Radiation: ITV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient with a NSCLC, non-resected, non-metastatic including a parenchyma portion Age >= 18 years PS <=2 CT-scan within 3 months at inclusion PET-scan within 3 months at inclusion Respiratory functional exploration within 3 months at inclusion estimated V20 (by radiotherapist)< 35% on conventional pre-radiotherapy imaging Tumor T0 to T4, M0; N1, N2 ou N3 by isolateral supra-clavicular involvement Measurable disease according to RECIST criteria 1.1 Curative intent Chest conventional radiation therapy Radiation indication validated by a multidisciplinary meeting Adequate contraceptive method for the whole study duration and for up to 28 days after the end of radiation Mandatory affiliation with a health insurance company Patients must provide dated & written consent Exclusion Criteria: Prior surgery for NSCLC NSCLC nearby pulmonary apex or strictly intra-thoracic with no intra-parenchyma portion Metastatic disease or N3 contralateral lymph node History of chest irradiation History of known increased intrinsic radiosensibility Hypersensibility to active substance or excipient of fluoro-deoxyglucose-18F Life expectancy < 6 months Patient with a concurrent malignancy or with a history of malignancy (excepted adequately treated basal cell skin carcinoma or cervical squamous cell carcinoma or other malignancies free of the disease for at least 5 years) Pregnant or breastfeeding women Psychological, sociological or geographical conditions that would limit compliance with study requirements Patient deprived of freedom Patient has concomitant participation to an other investigational study

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: midP arm<br>Patients treated with midP radiotherapy strategy. | Radiation: mid-position radiation strategy<br>* The midP strategy defines the target as the time weighted average tumor position (mid-position) plus an additional margin, computed specifically for each patient, that takes into account the tumor motion in each direction. This strategy can help to safely reduce toxicity while preserving treatment efficacy<br>|
| Active Comparator: ITV arm<br>Patient treated with radiotherapy ITV strategy | Radiation: ITV<br>* The ITV strategy is the conventional one. It consists in defining the target as the volume covering the whole tumor motion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1 year Progression Free Survival rate | Efficacy evaluation of the midP strategy in comparison with ITV strategy in patient with locally advanced, non-resected NSCL cancer treated with radiotherapy | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local tumor control rate |  | 1 year and 2 years after the end of irradiation | 
| Overall survival |  | 1 year and 2 years post irradiation | 
| To determine acute and late pulmonary toxicity in the 2 arms, including respiratory functional exploration |  | Week1; Week 2; Week3; Week4; Week5; Week6; Week7 during the radiation, then 4 weeks, 3 months; 6 months ,one year and 2 years after the irradiation beginning |