Safety of a Boost (CXB or EBRT) in Combination With Neoadjuvant Chemoradiotherapy for Early Rectal Adenocarcinoma
- Conditions
- Interventions
- Registration Number
- NCT02505750
- Lead Sponsor
- Centre Antoine Lacassagne
- Brief Summary
The investigators propose to conduct a randomised study on cT2, cT3a-b tumours less than 5 cm using two different techniques of radiotherapy boost following neoadjuvant chemoradiotherapy (nCRT) (CAP45): EBRT (9 Gy/5 fractions) or CXB (90 Gy/3 fractions). The endpoint will be organ preservation at 3 years without non-salvageable local pelvic recurrence. The p...
- Detailed Description
Rationale - current state of knowledge Current guidelines for cT2-T3 (clinical stage T2 and T3) low and middle rectal cancer recommend radical total mesorectal excision (TME) surgery that may involves permanent stoma or a low anterior resection with sometimes poor bowel function.
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Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 236
- Adenocarcinoma of the rectum classified clinically T2, T3a, T3b (penetration in the mesorectal fat between 1 to 5 mm) by TNM classification (Tumour Node Metastase), < 5 cm largest diameter, < half rectal circumference (by MRI staging), N0-N1 (any node < 8 mm diameter on MRI), M0
- Operable patient
- Tumour accessible to endocavitary contact X-Ray Brachytherapy with a distance from the lower tumour border to the anal verge ≤ 10cm
- 18 years or above
- No comorbidity preventing treatment
- Adequate birth control
- Patient having read the information note and having signed the informed consent
- Health care insurance available
- Follow-up possible
- Inoperable patient
- T1, T3cd, T4, T≥ 5cm, T≥ ½ circumference
- Patient N2 at diagnosis or N1 with any node > 8 mm diameter
- Patient presenting metastasis at diagnosis
- Previous pelvic irradiation
- Tumour with extramural vascular invasion
- Simultaneous progressive cancer
- Tumour invading external anal sphincter and within 1 mm, and the levator muscle
- Patient unable to receive CXB or CRT
- Tumour with poor differentiation (G3)
- People particularly vulnerable as defined in Articles L.1121-5 to -8 of the French Healthcare Code, including: person deprived of freedom by an administrative or judicial decision, adult being the object of a legal protection measure or outside state to express their consent, pregnant or breastfeeding women
- Any significant concurrent medical illness that in the opinion of the investigator would preclude protocol therapy
- Patient with history of poor compliance or current or past psychiatric conditions or severe acute or chronic medical conditions that would interfere with the ability to comply with the study protocol
- Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment within 28 days prior to the first dose of study treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description EBRT 45 Gy/capecitabine + CXB boost 3D conformal EBRT Arm B divided in 2 subgroups depending on the tumour diameter: B1: If the tumour is \< 3 cm, a CXB boost dose (90Gy/3 fractions/4 weeks) will be initially delivered to the tumour. After 2 weeks rest, patients will receive 3D conformal EBRT 45 Gy (1.8 Gy/fraction/5 weeks) with concurrent chemotherapy using capecitabine (825 mg/m2 bid, on radiation days). Clinical evaluation will be performed 3 weeks after the end of irradiation (week 14) and will guide the final strategy (surgery or W-W) as in arm A. B2: If the tumour is ≥ 3 cm, patients will receive EBRT first 45 Gy (1.8 Gy/fraction/5 weeks) with concurrent chemotherapy using capecitabine (825 mg/m2 bid, on radiation days). A CXB boost dose (90 Gy/3 fractions/4 weeks) will be delivered to residual tumour, after a rest of 2 weeks. On week 14 after the start of treatment, the tumour response evaluation will guide the final strategy (surgery or W-W) as in arm A. Adjuvant chemotherapy will be left to institution choice. EBRT 45 Gy/capecitabine + CXB boost Contact X-ray brachytherapy 50 kV Arm B divided in 2 subgroups depending on the tumour diameter: B1: If the tumour is \< 3 cm, a CXB boost dose (90Gy/3 fractions/4 weeks) will be initially delivered to the tumour. After 2 weeks rest, patients will receive 3D conformal EBRT 45 Gy (1.8 Gy/fraction/5 weeks) with concurrent chemotherapy using capecitabine (825 mg/m2 bid, on radiation days). Clinical evaluation will be performed 3 weeks after the end of irradiation (week 14) and will guide the final strategy (surgery or W-W) as in arm A. B2: If the tumour is ≥ 3 cm, patients will receive EBRT first 45 Gy (1.8 Gy/fraction/5 weeks) with concurrent chemotherapy using capecitabine (825 mg/m2 bid, on radiation days). A CXB boost dose (90 Gy/3 fractions/4 weeks) will be delivered to residual tumour, after a rest of 2 weeks. On week 14 after the start of treatment, the tumour response evaluation will guide the final strategy (surgery or W-W) as in arm A. Adjuvant chemotherapy will be left to institution choice. EBRT 45 Gy/capecitabine + EBRT boost 3D conformal EBRT 3D conformal EBRT 45 Gy (1.8Gy/fraction/5 weeks) with concurrent chemotherapy using capecitabine (825 mg/m2 bid, on radiation days). A cone down EBRT targeting the GTV will deliver a boost dose of 9 Gy in 5 fractions. On week 14 after the start of treatment, the tumour response evaluation will guide the final strategy: surgery (radical TME or local excision) or watch-and-wait (W-W). EBRT 45 Gy/capecitabine + EBRT boost Capecitabine 3D conformal EBRT 45 Gy (1.8Gy/fraction/5 weeks) with concurrent chemotherapy using capecitabine (825 mg/m2 bid, on radiation days). A cone down EBRT targeting the GTV will deliver a boost dose of 9 Gy in 5 fractions. On week 14 after the start of treatment, the tumour response evaluation will guide the final strategy: surgery (radical TME or local excision) or watch-and-wait (W-W). EBRT 45 Gy/capecitabine + CXB boost Capecitabine Arm B divided in 2 subgroups depending on the tumour diameter: B1: If the tumour is \< 3 cm, a CXB boost dose (90Gy/3 fractions/4 weeks) will be initially delivered to the tumour. After 2 weeks rest, patients will receive 3D conformal EBRT 45 Gy (1.8 Gy/fraction/5 weeks) with concurrent chemotherapy using capecitabine (825 mg/m2 bid, on radiation days). Clinical evaluation will be performed 3 weeks after the end of irradiation (week 14) and will guide the final strategy (surgery or W-W) as in arm A. B2: If the tumour is ≥ 3 cm, patients will receive EBRT first 45 Gy (1.8 Gy/fraction/5 weeks) with concurrent chemotherapy using capecitabine (825 mg/m2 bid, on radiation days). A CXB boost dose (90 Gy/3 fractions/4 weeks) will be delivered to residual tumour, after a rest of 2 weeks. On week 14 after the start of treatment, the tumour response evaluation will guide the final strategy (surgery or W-W) as in arm A. Adjuvant chemotherapy will be left to institution choice.
- Primary Outcome Measures
Name Time Method Rate of rectum preservation either with local excision or watch and wait strategy after neoadjuvant treatment without non salvageable locally progressive disease at 3 years post treatment, or permanent stoma. 3 years post treatment The primary analysis will take place when approximately 138 events have occurred.
The evaluation of the rate of rectum preservation without progressive local disease at 3 years will be performed using a Log rank test stratified by center.
- Secondary Outcome Measures
Name Time Method Clinical Complete Response (assessed by digital rectal examination, endoscopy with photos and MRI) Week 14 Overall Survival 3 years post treatment Time between date of randomisation and date of death due to any causes. Patients who were not reported as having died at the time of the study will be censored at the date they were last known to be alive
Disease-free survival 3 years post treatment Time between date of randomisation to time of recurrence, either local or distant metastasis or death due to any cause). Patients without an event will be censored at last date the patient was known to be disease-free. Recurrence of rectal cancer will be based on tumour assessment made by investigator
Tumour regression score on the operative specimen week 24
Trial Locations
- Locations (20)
Centre d'oncologie et de radiothérapie Mâcon
🇫🇷Mâcon, France
Aarhus University Hospital
🇩🇰Aarhus, Denmark
Hospices Civils de Lyon - Hôpital de la Croix Rousse
🇫🇷Lyon, France
Institut Paoli Calmette
🇫🇷Marseille, France
Centre Azuréen de Cancérologie
🇫🇷Mougins, France
Hôpital La Timone - AP-HM
🇫🇷Marseille, France
Centre Léon Bérard
🇫🇷Lyon, France
Centre de Haute Energie
🇫🇷Nice, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Hospices Civils de Lyon - Centre Hospitalier Lyon-Sud
🇫🇷Pierre Bénite, France
Institut de Cancérologie Lucien Neuwirth
🇫🇷Saint-Priest en Jarez, France
Clinique Charcot
🇫🇷Sainte Foy-Lès-Lyon, France
Hôpital de la Croix Rouge Française - Centre de Radiothérapie St Louis
🇫🇷Toulon, France
Centre de radiothérapie Bayard
🇫🇷Villeurbanne, France
Karolinska Institute
🇸🇪Stockholm, Sweden
Spire Hull and East Riding Hospital
🇬🇧Hull, United Kingdom
University of Uppsala
🇸🇪Uppsala, Sweden
Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
Royal Surrey County Hospital
🇬🇧Guildford, United Kingdom
University Hospital
🇬🇧Nottingham, United Kingdom
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