Etude : RTEP7 / IFCT-1402

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Acronyme / Nom
Situation thérapeutique
Cadre réglementaire
Présentation de l'étude
Acronyme / Nom : RTEP7 / IFCT-1402

Situation thérapeutique : Métastatique ou localement avancé

Traitement : Radiothérapie

Cadre réglementaire : RIPH1

Dernière MÀJ : 13/12/2021
CIM10 - Localisation(s)
Informations principales
Titre : Randomized Phase II-III Study of Personalized Radiotherapy Dose Redistribution in Patients With Inoperable Stage III Non-small Cell Lung Cancer and a Persistent FDG Uptake at 42 Grays During Concomitant Radio-chemotherapy

Spécialité : Organes respiratoires et intrathoraciques
Localisation : C34 - Tumeur maligne des bronches et du poumon
Informations complémentaires
Schéma : Primary objective:
To determine whether tumour RT dose escalated up to 74 Gy in 6.6 weeks can improve the disease Local Regional Control (LRC) rate at 15 months (1 year after completion of RCT) by adapting RT target volume to the metabolic response as assessed on FDG-PET/CT performed at 42 Gy of concomitant RCT in stage III NSCLC and warrant more extensive phase III study.

Secondary objectives:
- Overall survival (OS) at M9, M15, M27, M39 visits (6 months, 1, 2 and 3 years post-RCT) primary objective of phase III (D1 is the inclusion/randomization date),
- Evaluation of LCR at M9, M27, M39 visits (6 months, 2 and 3 years post-RCT),
- Evaluation of immediate toxicity at M9 (6 months post-RCT) and long term toxicity at M15, M27, M39 visits (1, 2 and 3 years post-RCT),
- Progression-free survival at M15, M27, M39 visits (1, 2 and at 3 years post-RCT),
- Predictive value at M9, M15, M27, M39 visits (6 months, 1, 2 and 3 years post-RCT) of 18F-FDG PET performed at 42 Gy of RCT,
- Impact of the relative change in FDG uptake (SUVmax) and metabolic tumour volume between baseline and per-RT (42 Gy) in terms of LRC at M15, M27, M39 follow-up visits (1, 2 and 3-year post-RCT),
- Impact of 4D CT and 4D FDG-PET/CT on delineation of the Planning Target Volume (PTV).

Study design:
- Open, double arm, randomized phase II of a phase II-III study (phase II/III with accrual suspension after phase II patients accrued),
- Patients will be stratified by center (according to IMRT vs bifractionated RT),
- The registration date (D1) is the inclusion/randomization date. M9, M15, M27 and M39 follow-up visits correspond to 6 months, 1, 2 and 3 years after completion of RCT.
- Eligible patients will be allocated to one of 2 treatment groups:
· Arm A: Patients in the experimental arm will receive an individualized RT prescription up to a total dose of 74 Gy given in 6.6 weeks if they have a positive FDG-PET42Gy (about two thirds of pts are expected as positive ie 50/75; Vera, EJNMMI2014). An initial dose of 50 Gy will be delivered in 5 weeks (single daily fractions of 2 Gy), then an additional dose up to 24 Gy will be delivered over 1.6 week using a twice-a-day (BID) fractionated RT: 2.0 Gy in the initial Planning Target Volume (PTV) plus a 1.0 Gy fraction at least 6 hours later in the biological target volume (BTV). The BTV will be delineated on a FDG-PET scan acquired after an initial dose of 42 Gy ± 2 Gy (FDG-PET2), i.e. after 21 fractions. If IMRT is applied, a single daily Simultaneous Integrated Boost (SIB) will be allowed.
· Arm B: Patients in the standard arm will receive a single prescription of 66 Gy in 33 fractions in 6.6 weeks, with 2 Gy fractions given once daily, 5 days a week, without target volume reduction or adaptation (whatever the FDG-PET result).
- In both arms, all patients will undergo 2 cycles of induction CT (based platinum salts) and a curative RCT. In both arms all fields must be treated daily. The total
dose will be prescribed so that the total Mean Lung Dose (MLD) is ≤ 20 Gy and V20 < 30%, and doses to other organs at risk (oesophagus, heart and spine)
meet the standard limits. Respiratory gating and IMRT will be optional. A biological ancillary study (RTEP7 bio) will be performed.
This funding request concerns only the phase II of this trial, therefore we do not present the exact design of the phase III part of the study in this document. For Phase III, all the patients included in phase II remain evaluable for survival.

Phase : II/III

Stade : Localement avancé

1, 2, 3, 4, X
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Male or female patients,
- Age over 18 years and below 75-year-old,
- Good general condition: WHO performance status ≤ 1,
- Histological evidence of non-small cell lung cancer,
- Measureable tumour according to RECIST 1.1 evaluation criteria,
- Mediastinoscopy or endobronchial ultrasound to prove the histological stage N2/N3,
- Patient eligible to curative-intent radio-chemotherapy,
*Absence of pleural involvement, of pulmonary or extra-thoracic metastatic localisation,
*Absence of co-morbidity contra-indicating radio-chemotherapy,
- Lung function: FEV1 ≥ 40% of theoretical value and DLCO/VA ≥ 60% of theoretical value and PaO2 ≥ 60 mm Hg,
- Tumour FDG uptake higher than mediastinal background noise on baseline PET/CT,
- Haematological parameters:
*Neutrophil count ≥ 1.5x109/L and platelet count ≥ 100x109/L,
*Haemoglobin ≥ 9 g/dL,
- Provisional RT plan confirming that the dose objectives (minimal dose of 62.7 Gy (95% of the prescribed dose) in 98% of target volumes and 70.3 Gy for the "boosted" volume at 74 Gy) and constraints (lungs, spinal cord) are met (ICRU83),
- Estimated creatinine clearance ≥ 60 mL/min,
- Signed informed consent
- Affiliated or beneficiary of a social benefit system

Critères de non-inclusion : - Histology other than non-small cell lung cancer,
- Absence of FDG uptake on FDG-PET/CT scan before induction chemotherapy,
- Patients for whom curative radiotherapy is not indicated (tumour extension, metastases, general condition, co-morbidities),
- Significant interstitial disease on CT scan,
- Previous neoplastic disease of less than 5 years duration or progressive (without basal cell carcinoma of the skin, in situ carcinoma of the cervix),
- Previous thoracic radiotherapy,
- Patient enrolled in another therapeutic trial,
- Pregnant women or women of child-bearing potential or breast feeding mothers,
- Adult subjects who are under protective custody or guardianship,
- Patient unable to comply with the specific obligations of the study (geographic, social or physical reasons),
- Uncontrolled diabetes with blood glucose ≥10 mmol/L,
- Hypersensitivity to the active substance (FDG) or to any of the excipients,
- Patients unable to understand the purpose of the study (language, etc.)
Informations relatives au promoteur
Promoteur :
Centre Henri Becquerel
Type de sponsor : Institutionnel
76000 ROUEN

Coordonnateur :
Pierre VERA
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre Oscar Lambret - 3 Rue Frédéric Combemale - 59000 LILLE

Investigateur :
Docteur Hélène GAUTIER

Unité Intégrée de Recherche Clinique

Statut de l'essai : CLOS

MAJ : 15/09/2021