Clinical trial · Interventional
Safety of a Boost (CXB or EBRT) in Combination With Neoadjuvant Chemoradiotherapy for Early Rectal Adenocarcinoma
European Phase III Study Comparing a Radiation Dose Escalation Using 2 Different Approaches : External Beam Radiation Therapy Versus Endocavitary Radiation Therapy With Contact X-ray Brachytherapy 50 kiloVolts (kV) for Patients With Rectal Adenocarcinoma
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Rectal Neoplasms | Rectal Neoplasm | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| 3D conformal EBRT | Radiation | — | UNRESOLVED |
| Capecitabine | Drug | Capecitabine | ALIAS |
| Contact X-ray brachytherapy 50 kV | Device | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- ACTIVE_COMPARATOR
- label
- EBRT 45 Gy/capecitabine + EBRT boost
- description
- 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).
- interventionNames
- Radiation: 3D conformal EBRT
- Drug: Capecitabine
- type
- EXPERIMENTAL
- label
- EBRT 45 Gy/capecitabine + CXB boost
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (2)
- DERIVEDSun Myint A, Rao C, Barbet N, Thamphya B, Pace-Loscos T, Schiappa R, Magne N, Martel-Lafay I, Mineur L, Deberne M, Zilli T, Dhadda A, Gerard JP. The safety and efficacy of total mesorectal excision (TME) surgery following dose-escalation: Surgical outcomes from the organ preservation in early rectal adenocarcinoma (OPERA) trial, a European multicentre phase 3 randomised trial (NCT02505750). Colorectal Dis. 2023 Nov;25(11):2160-2169. doi: 10.1111/codi.16773. Epub 2023 Oct 13. PMID 37837240
- DERIVEDGerard JP, Barbet N, Schiappa R, Magne N, Martel I, Mineur L, Deberne M, Zilli T, Dhadda A, Myint AS; ICONE group. Neoadjuvant chemoradiotherapy with radiation dose escalation with contact x-ray brachytherapy boost or external beam radiotherapy boost for organ preservation in early cT2-cT3 rectal adenocarcinoma (OPERA): a phase 3, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023 Apr;8(4):356-367. doi: 10.1016/S2468-1253(22)00392-2. Epub 2023 Feb 16. PMID 36801007