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

NCT02505750 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: 2014/142014-A01851-46
• Study Type: interventional
• Target: 148
• Locations: 3 countries
• Sites: 18

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 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

Rectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  3 years post treatment

Secondary Outcomes (4)

• Clinical Complete Response (assessed by digital rectal examination, endoscopy with photos and MRI)

  Week 14

• Overall Survival

  3 years post treatment

• Disease-free survival

  3 years post treatment

• Tumour regression score on the operative specimen

  week 24

Other Outcomes (4)

• Rate of sphincter conservation

  3 years post treatment

• Treatment toxicity

  3 years post treatment

• Bowel function

  3 years post treatment

Study Arms (2)

EBRT 45 Gy/capecitabine + EBRT boost

ACTIVE COMPARATOR

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).

Radiation: 3D conformal EBRT; Drug: Capecitabine

EBRT 45 Gy/capecitabine + CXB boost

EXPERIMENTAL

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.

Radiation: 3D conformal EBRT; Device: Contact X-ray brachytherapy 50 kV; Drug: Capecitabine

Interventions

3D conformal EBRT RADIATION

External Beam Radiation Therapy

EBRT 45 Gy/capecitabine + CXB boost; EBRT 45 Gy/capecitabine + EBRT boost

Contact X-ray brachytherapy 50 kV DEVICE

EBRT 45 Gy/capecitabine + CXB boost

Capecitabine DRUG

EBRT 45 Gy/capecitabine + CXB boost; EBRT 45 Gy/capecitabine + EBRT boost

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (18)

Clinique de la Sauvegarde

Lyon, Auvergne-Rhône-Alpes, 69009, France

Location

CHRU Besançon

Besançon, Bourgogne-Franche-Comté, 25030, France

Location

Centre Jean Godinot

Reims, Champagne-Ardenne, 51726, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Centre d'oncologie et de radiothérapie Mâcon

Mâcon, 71000, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hospices Civils de Lyon - Centre Hospitalier Lyon-Sud

Pierre-Bénite, 69495, France

Location

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, 42270, France

Location

Clinique Charcot

Sainte-Foy-lès-Lyon, 69110, France

Location

Hôpital de la Croix Rouge Française - Centre de Radiothérapie St Louis

Toulon, 83100, France

Location

Centre de radiothérapie Bayard

Villeurbanne, 69100, France

Location

Hôpitaux Universitaires de Genève

Geneva, CG-1211, Switzerland

Location

Royal Surrey County Hospital

Guildford, GU2 7XX, United Kingdom

Location

Spire Hull and East Riding Hospital

Hull, HU10 7AZ, United Kingdom

Location

Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, L9 7BA, United Kingdom

Location

Christie Hospital

Manchester, M204BX, United Kingdom

Location

University Hospital

Nottingham, NG5 8RX, United Kingdom

Location

Related Publications (2)

• Sun 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 DERIVED

• Gerard 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 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Jérôme DOYEN, M.D, PhD

  Centre Antoine Lacassagne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2015
• First Posted: July 22, 2015
• Study Start: June 24, 2015
• Primary Completion: June 7, 2023
• Study Completion (Estimated): June 1, 2030
• Last Updated: September 29, 2025

Record last verified: 2025-09

Locations

GB (5); FR (12); CH (1)