Safety of a Boost (CXB or EBRT) in Combination With Neoadjuvant Chemoradiotherapy for Early Rectal Adenocarcinoma

• Status: Active, not recruiting
• Trial end date: 2022-09-01
• Target enrollment: 0
• Participant gender: All

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 proof of this concept will be of most benefit for all patients but especially for the elderly who usually are not fit for or keen to undergo major surgery.

The hypothesis of this study is to determine whether the addition of an endocavitary boost with CXB after standard treatment with nCRT, increases the chance of rectum and anus preservation by 20%-unites in early rectal adenocarcinoma without locally progressive disease (organ preservation in control arm 20%, in experimental arm 40%).

Main objective To demonstrate that neoadjuvant chemoradiotherapy in combination with a boost given with CXB (Arm B) is superior to the same neoadjuvant therapy plus a boost with EBRT alone (Arm A) in terms of rectum (organ) preservation without non salvageable local disease at 3 years post treatment start, or permanent deviating stoma.

Study Design Open-label, phase III, prospective, multi-centre, international, randomised 1:1, 2 arm study designed to evaluate the efficacy of a CXB boost versus an EBRT boost.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre Antoine Lacassagne
• Collaborators: Aarhus University Hospital; Centre Azuréen de Cancérologie; Centre de Haute Energie; Centre de radiothérapie Bayard; Centre Leon Berard; Centre Oncologie Radiothérapie de Mâcon; Clinique Charcot; Hôpital de la Croix-Rousse; Hôpital de la Timone; Hospices Civils de Lyon; Institut de Cancérologie Lucien Neuwirth; Institut Paoli-Calmettes; Karolinska Institutet; Nottingham University Hospitals NHS Trust; Royal Surrey County Hospital; Royal Surrey County Hospital NHS Foundation Trust; Spire Hull and East Riding Hospital; The Clatterbridge Cancer Centre NHS Foundation Trust; Uppsala University Hospital
• Treatments: Capecitabine

Criteria

Inclusion Criteria:

1. 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

2. Operable patient

3. Tumour accessible to endocavitary contact X-Ray Brachytherapy with a distance from the lower tumour border to the anal verge ≤ 10cm

4. 18 years or above

5. No comorbidity preventing treatment

6. Adequate birth control

7. Patient having read the information note and having signed the informed consent

8. Health care insurance available

9. Follow-up possible

Exclusion Criteria:

1. Inoperable patient

2. T1, T3cd, T4, T≥ 5cm, T≥ ½ circumference

3. Patient N2 at diagnosis or N1 with any node > 8 mm diameter

4. Patient presenting metastasis at diagnosis

5. Previous pelvic irradiation

6. Tumour with extramural vascular invasion

7. Simultaneous progressive cancer

8. Tumour invading external anal sphincter and within 1 mm, and the levator muscle

9. Patient unable to receive CXB or CRT

10. Tumour with poor differentiation (G3)

11. 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

12. Any significant concurrent medical illness that in the opinion of the investigator would preclude protocol therapy

13. 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

14. Concurrent enrolment in another clinical trial using an investigational anti-cancer treatment within 28 days prior to the first dose of study treatment