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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02505750
Recruitment Status : Active, not recruiting
First Posted : July 22, 2015
Last Update Posted : October 26, 2021
Sponsor:
Collaborators:
Centre de Haute Energie
Centre Azuréen de Cancérologie
Hôpital de la Croix-Rousse
Institut Paoli-Calmettes
Hôpital de la Timone
Centre de radiothérapie Bayard
Centre Oncologie Radiothérapie de Mâcon
Centre Leon Berard
Hospices Civils de Lyon
Clinique Charcot
Institut de Cancérologie Lucien Neuwirth
The Clatterbridge Cancer Centre NHS Foundation Trust
Spire Hull and East Riding Hospital
Nottingham University Hospitals NHS Trust
Royal Surrey County Hospital NHS Foundation Trust
Uppsala University Hospital
Karolinska Institutet
Aarhus University Hospital
Information provided by (Responsible Party):
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 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.


Condition or disease Intervention/treatment Phase
Rectal Neoplasms Radiation: 3D conformal EBRT Device: Contact X-ray brachytherapy 50 kV Drug: Capecitabine Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 236 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 24, 2015
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: EBRT 45 Gy/capecitabine + EBRT boost

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
External Beam Radiation Therapy

Drug: Capecitabine
Experimental: EBRT 45 Gy/capecitabine + CXB boost

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
External Beam Radiation Therapy

Device: Contact X-ray brachytherapy 50 kV
Drug: Capecitabine



Primary Outcome Measures :
  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. [ Time Frame: 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 :
  1. Clinical Complete Response (assessed by digital rectal examination, endoscopy with photos and MRI) [ Time Frame: Week 14 ]
  2. Overall Survival [ Time Frame: 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

  3. Disease-free survival [ Time Frame: 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

  4. Tumour regression score on the operative specimen [ Time Frame: week 24 ]

Other Outcome Measures:
  1. Rate of sphincter conservation [ Time Frame: 3 years post treatment ]
  2. Treatment toxicity [ Time Frame: 3 years post treatment ]
    Early and late toxicity by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0.

  3. Bowel function [ Time Frame: 3 years post treatment ]
    Bowel function by modified Low Anterior Resection Score (LARS)

  4. Quality of Life [ Time Frame: 3 years post treatment ]
    Quality of life questionnaire (QLQ): QLQ-C30 and colorectal (CR) QLQ-CR29 questionnaires



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02505750


Locations
Show Show 20 study locations
Sponsors and Collaborators
Centre Antoine Lacassagne
Centre de Haute Energie
Centre Azuréen de Cancérologie
Hôpital de la Croix-Rousse
Institut Paoli-Calmettes
Hôpital de la Timone
Centre de radiothérapie Bayard
Centre Oncologie Radiothérapie de Mâcon
Centre Leon Berard
Hospices Civils de Lyon
Clinique Charcot
Institut de Cancérologie Lucien Neuwirth
The Clatterbridge Cancer Centre NHS Foundation Trust
Spire Hull and East Riding Hospital
Nottingham University Hospitals NHS Trust
Royal Surrey County Hospital NHS Foundation Trust
Uppsala University Hospital
Karolinska Institutet
Aarhus University Hospital
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Responsible Party: Centre Antoine Lacassagne
ClinicalTrials.gov Identifier: NCT02505750    
Other Study ID Numbers: 2014/14
2014-A01851-46 ( Other Identifier: Agence National de Sécurité du Médicament et des produits de santé )
First Posted: July 22, 2015    Key Record Dates
Last Update Posted: October 26, 2021
Last Verified: October 2021
Additional relevant MeSH terms:
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Adenocarcinoma
Rectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents