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Optimisation of Response for Organ Preservation in Rectal Cancer : Neoadjuvant Chemotherapy and Radiochemotherapy vs. Radiochemotherapy (GRECCAR12)

Primary Purpose

Rectal Cancer

Status
Active
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Neoadjuvant chemotherapy Folfirinox, 4 cycles
50 Gy, 2 Gy/session; 25 fractions
Local excision in good responders
Rectal excision in bad responders
Capecitabine
Sponsored by
University Hospital, Bordeaux
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Rectal Cancer focused on measuring Organ preservation, Local excision, Radiochemotherapy, Neoadjuvant chemotherapy, Folfirinox, Tumour response

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Rectal adenocarcinoma
  • cT2T3
  • cN0-1 (≤ 3 positive lymph nodes or size ≤8mm)
  • Tumour size ≤4 cm
  • Location ≤10 cm from the anal verge
  • No distant metastasis
  • Patient ≥18 years
  • ECOG ≤2
  • Effective contraception during the study
  • Patient and doctor have signed informed consent

Exclusion Criteria:

  • T1 or T4
  • Tumour size >4cm
  • N2 (>3 positive lymph nodes or size >8mm)
  • Tumour > 10 cm from the anal verge
  • Distant metastasis
  • Chronic intestinal inflammation and/or bowel obstruction
  • Contra indication for chemotherapy and/or radiotherapy
  • Previous pelvic radiotherapy or chemotherapy
  • Severe renal, hepatic insufficiency (serum creatinine<30ml/min)
  • Peripheral neuropathy > grade 1
  • Complete or partial Dihydropyrimidine deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)
  • Concomitant treatment with millepertuis, yellow fever vaccine, phenytoin or sorivudine (or chemically equivalent)
  • Pregnant or breast-feeding woman.
  • Persons deprived of liberty or under guardianship
  • Impossibility for compliance to follow-up

Sites / Locations

  • Service de Chirurgie Digestive, CHU Amiens Picardie
  • Service de Chirurgie Digestive, CHU de Besançon
  • Service de Chirurgie Digestive, Hôpital Saint-André - CHU de Bordeaux
  • Service de Chirurgie Digestive, Institut Bergonié
  • Service de Chirurgie Digestive, CHU Estaing - CHRU Clermont Ferrand
  • Service de Chirurgie Digestive, Hôpital Beaujon - APHP
  • Service de Chirurgie Digestive, Centre Georges François Leclerc - Dijon
  • Service de Chirurgie Digestive, Hôpital Albert Michallon - CHU de Grenoble
  • Service de Chirurgie Digestive, Centre Oscar Lambret - Lille
  • Service de Chirurgie Digestive, Centre Léon Bérard - Lyon
  • Service de Chirurgie Digestive, Hôpital Lyon Sud - CHU Lyon
  • Service de Chirurgie Digestive, CHU de la Timone - Marseille
  • Service de Chirurgie Digestive, Institut Paoli Calmette - Marseille
  • Service de Chirurgie Digestives, Hôpital Européen de Marseille
  • Service de Chirurgie Digestive, Institut du Cancer de Montpellier
  • Service d'Oncologie et Radiothérapie, Centre Azuréen de Cancérologie
  • Service de Chirurgie Digestive,Institut de Cancérologie de Lorraine
  • Service de Chirurgie Digestive, Hôtel Dieu - CHU de Nantes
  • Service de Chirurgie Digestive, CHU Carémeau - Nîmes
  • GH Paris Saint Joseph
  • Service de Chirurgie Digestive et Oncologique, Hôpital Bicêtre - APHP
  • Service de Chirurgie Digestive, Hôpital les Diaconnesses
  • Service de Chirurgie Digestive, Hôpital Saint-Antoine - APHP
  • Service de Chirurgie Digestive, Hôpital Saint-Louis - APHP Paris
  • Service de Chirurgie Digestive, Hôpital Pontchaillou - CHU Rennes
  • Service de Chirurgie Digestive, Hôpital Charles Nicolle - CHU de Rouen
  • Service de Chirurgie Digestive, Hôpital Purpan - CHU de Toulouse
  • Service de chirurgie digestive, CHRU de Nancy -Hôpital de Brabois
  • Département de chirurgie digestive, Institut Gustave Roussy

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Chemotherapy and Radiochemotherapy

Radiochemotherapy

Arm Description

Neoadjuvant chemotherapy Folfirinox, 4 cycles: oxaliplatin: 85 mg/m2 irinotecan: 180 mg/m² folinic acid: 400 mg/m2 (DL form) or 200 mg/m2 (L form) 5FU: 2400 mg/m2 Radiochemotherapy : 2 to 4 weeks after chemotherapy, 5 weeks (50 Gy, 2 Gy/session; 25 fractions) + capecitabine (1600 mg/m2 daily 5 days/7)

Radiochemotherapy: 5 weeks (50 Gy, 2 Gy/session ; 25 fractions) + capecitabine (1600 mg/m2 daily 5 days/7, excluding weekends)

Outcomes

Primary Outcome Measures

Rate of organ preservation and absence of stoma
Number of patients with organ preservation and absence of stoma at 1 year after surgery

Secondary Outcome Measures

Compliance to treatment
Number of patients receiving full neoadjuvent treatment and the allocated surgery
Tolerance to treatment
Number of patients with adverse events
Rate of clinical complete response
To determine the rate of grade 1 : no tumor at digital examination
Rate of radiological response
To determine the rate of tumor ≤ 2 cm with TRG1-3 at MRI
Rate of complete pathologic response
To determine the rate of ypT0
Correlation between radiological and clinical response
To analyse the correlation between radiological response ( tumor ≤ 2 cm with TRG1-3 at MRI) and clinical response (grade 1)
Correlation between radiological (radiomic analysis) and pathologic response
To analyse the correlation between radiological response ( tumor ≤ 2 cm with TRG1-3 at MRI) and pathological response (ypT0)
Rate of curative surgery
To determine the rate of R0 resection
Surgical morbidity
To analyse the cumulative Clavien-Dindo at 1 year
Quality of life
To examine score of questionnaires : QLQ CR-30, QLQ CR-29
Local recurrence
To determine the rate of local recurrence at 3 years
Overall survival
To determine the rate of overall survival at 3 years
Disease-free survival
To determine the rate of disease-free survival at 3 years

Full Information

First Posted
July 6, 2015
Last Updated
October 24, 2023
Sponsor
University Hospital, Bordeaux
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1. Study Identification

Unique Protocol Identification Number
NCT02514278
Brief Title
Optimisation of Response for Organ Preservation in Rectal Cancer : Neoadjuvant Chemotherapy and Radiochemotherapy vs. Radiochemotherapy
Acronym
GRECCAR12
Official Title
Optimisation of Response for Organ Preservation in Rectal Cancer : Neoadjuvant Chemotherapy and Radiochemotherapy vs. Radiochemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 28, 2016 (Actual)
Primary Completion Date
June 9, 2022 (Actual)
Study Completion Date
January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Standard treatment of rectal cancer is rectal excision with neoadjuvant radiochemotherapy. A new concept suggests organ preservation as an alternative to rectal excision in good responders after neoadjuvant radiochemotherapy to decrease surgical morbidity and increase quality of life. The rational is the fact that 15% of patients have sterilized tumours after radiochemotherapy for T3T4 rectal cancer. The French GRECCAR 2 trial is the first phase III trial investigating this strategy: patients with T2T3 low rectal carcinomas (size ≤4 cm) received 50 Gy with capecitabine and good clinical responders (≤2 cm) were randomized between local and rectal excision. The main findings were: the rate of complete pathologic response was higher after radiochemotherapy for small T2T3 than for T3T4 tumours (40% vs 15% ypT0) and good pathologic responders (ypT0-1) were associated with zero positive mesorectal nodes. The objective of the new trial is to increase the proportion of patients treated with organ preservation by optimizing tumour response. As compared to Folfiri, tritherapy Folfirinox has been shown to enhance the response rate. In patients with colorectal metastases, response rate and R0 resection were twice higher, resulting in improved survival. Folfirinox also increases response and chance of R0 resection rates in initially unresectable colorectal metastases, compared to standard or intensified bi-chemotherapy regimens. Adding two months of neoadjuvant chemotherapy (Folfirinox) before radiochemotherapy, the investigators expect to increase chance of organ preservation rate, as compared to radiochemotherapy alone.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
Keywords
Organ preservation, Local excision, Radiochemotherapy, Neoadjuvant chemotherapy, Folfirinox, Tumour response

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
218 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Chemotherapy and Radiochemotherapy
Arm Type
Experimental
Arm Description
Neoadjuvant chemotherapy Folfirinox, 4 cycles: oxaliplatin: 85 mg/m2 irinotecan: 180 mg/m² folinic acid: 400 mg/m2 (DL form) or 200 mg/m2 (L form) 5FU: 2400 mg/m2 Radiochemotherapy : 2 to 4 weeks after chemotherapy, 5 weeks (50 Gy, 2 Gy/session; 25 fractions) + capecitabine (1600 mg/m2 daily 5 days/7)
Arm Title
Radiochemotherapy
Arm Type
Active Comparator
Arm Description
Radiochemotherapy: 5 weeks (50 Gy, 2 Gy/session ; 25 fractions) + capecitabine (1600 mg/m2 daily 5 days/7, excluding weekends)
Intervention Type
Drug
Intervention Name(s)
Neoadjuvant chemotherapy Folfirinox, 4 cycles
Intervention Description
oxaliplatin: 85 mg/m2 irinotecan: 180 mg/m² folinic acid: 400 mg/m2 (DL form) or 200 mg/m2 (L form) 5FU: 2400 mg/m2
Intervention Type
Radiation
Intervention Name(s)
50 Gy, 2 Gy/session; 25 fractions
Intervention Description
Radiochemotherapy 5 weeks
Intervention Type
Procedure
Intervention Name(s)
Local excision in good responders
Intervention Description
If local excision: Surveillance if ypT0-1 or ypT2Nx/cN0 (no lymph node at baseline imaging) Complementary rectal excision if ypT2Nx/cN1, ypT3 or R1.
Intervention Type
Procedure
Intervention Name(s)
Rectal excision in bad responders
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
1600 mg/m2 daily 5 days/7
Primary Outcome Measure Information:
Title
Rate of organ preservation and absence of stoma
Description
Number of patients with organ preservation and absence of stoma at 1 year after surgery
Time Frame
1 year after surgery
Secondary Outcome Measure Information:
Title
Compliance to treatment
Description
Number of patients receiving full neoadjuvent treatment and the allocated surgery
Time Frame
From beginning of neoadjuvant treatment until surgery, expected average 20 weeks after neoadjuvant treatment
Title
Tolerance to treatment
Description
Number of patients with adverse events
Time Frame
From beginning of neoadjuvant treatment until 1 year after surgery
Title
Rate of clinical complete response
Description
To determine the rate of grade 1 : no tumor at digital examination
Time Frame
At 8 weeks after neoadjuvant treatment
Title
Rate of radiological response
Description
To determine the rate of tumor ≤ 2 cm with TRG1-3 at MRI
Time Frame
At 8 weeks after neoadjuvant treatment
Title
Rate of complete pathologic response
Description
To determine the rate of ypT0
Time Frame
At surgery, expected average 10 weeks after neoadjuvant treatment
Title
Correlation between radiological and clinical response
Description
To analyse the correlation between radiological response ( tumor ≤ 2 cm with TRG1-3 at MRI) and clinical response (grade 1)
Time Frame
Between 8 to 10 weeks after neoadjuvant treatment
Title
Correlation between radiological (radiomic analysis) and pathologic response
Description
To analyse the correlation between radiological response ( tumor ≤ 2 cm with TRG1-3 at MRI) and pathological response (ypT0)
Time Frame
Between 8 to 10 weeks after neoadjuvant treatment
Title
Rate of curative surgery
Description
To determine the rate of R0 resection
Time Frame
At surgery, expected average 10 weeks after neoadjuvant treatment
Title
Surgical morbidity
Description
To analyse the cumulative Clavien-Dindo at 1 year
Time Frame
From surgery until 1 year of follow-up
Title
Quality of life
Description
To examine score of questionnaires : QLQ CR-30, QLQ CR-29
Time Frame
From randomization until 1 year after surgery
Title
Local recurrence
Description
To determine the rate of local recurrence at 3 years
Time Frame
From surgery until 3 years of follow-up
Title
Overall survival
Description
To determine the rate of overall survival at 3 years
Time Frame
From surgery until 3 years of follow-up
Title
Disease-free survival
Description
To determine the rate of disease-free survival at 3 years
Time Frame
From surgery until 3 years of follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Rectal adenocarcinoma cT2T3 cN0-1 (≤ 3 positive lymph nodes or size ≤8mm) Tumour size ≤4 cm Location ≤10 cm from the anal verge No distant metastasis Patient ≥18 years ECOG ≤2 Effective contraception during the study Patient and doctor have signed informed consent Exclusion Criteria: T1 or T4 Tumour size >4cm N2 (>3 positive lymph nodes or size >8mm) Tumour > 10 cm from the anal verge Distant metastasis Chronic intestinal inflammation and/or bowel obstruction Contra indication for chemotherapy and/or radiotherapy Previous pelvic radiotherapy or chemotherapy Severe renal, hepatic insufficiency (serum creatinine<30ml/min) Peripheral neuropathy > grade 1 Complete or partial Dihydropyrimidine deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL) Concomitant treatment with millepertuis, yellow fever vaccine, phenytoin or sorivudine (or chemically equivalent) Pregnant or breast-feeding woman. Persons deprived of liberty or under guardianship Impossibility for compliance to follow-up
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric RULLIER, Prof.
Organizational Affiliation
University Hospital Bordeaux, France
Official's Role
Principal Investigator
Facility Information:
Facility Name
Service de Chirurgie Digestive, CHU Amiens Picardie
City
Amiens
Country
France
Facility Name
Service de Chirurgie Digestive, CHU de Besançon
City
Besançon
Country
France
Facility Name
Service de Chirurgie Digestive, Hôpital Saint-André - CHU de Bordeaux
City
Bordeaux
Country
France
Facility Name
Service de Chirurgie Digestive, Institut Bergonié
City
Bordeaux
Country
France
Facility Name
Service de Chirurgie Digestive, CHU Estaing - CHRU Clermont Ferrand
City
Clermont-Ferrand
Country
France
Facility Name
Service de Chirurgie Digestive, Hôpital Beaujon - APHP
City
Clichy
Country
France
Facility Name
Service de Chirurgie Digestive, Centre Georges François Leclerc - Dijon
City
Dijon
Country
France
Facility Name
Service de Chirurgie Digestive, Hôpital Albert Michallon - CHU de Grenoble
City
La Tronche
Country
France
Facility Name
Service de Chirurgie Digestive, Centre Oscar Lambret - Lille
City
Lille
Country
France
Facility Name
Service de Chirurgie Digestive, Centre Léon Bérard - Lyon
City
Lyon
Country
France
Facility Name
Service de Chirurgie Digestive, Hôpital Lyon Sud - CHU Lyon
City
Lyon
Country
France
Facility Name
Service de Chirurgie Digestive, CHU de la Timone - Marseille
City
Marseille
Country
France
Facility Name
Service de Chirurgie Digestive, Institut Paoli Calmette - Marseille
City
Marseille
Country
France
Facility Name
Service de Chirurgie Digestives, Hôpital Européen de Marseille
City
Marseille
Country
France
Facility Name
Service de Chirurgie Digestive, Institut du Cancer de Montpellier
City
Montpellier
Country
France
Facility Name
Service d'Oncologie et Radiothérapie, Centre Azuréen de Cancérologie
City
Mougins
Country
France
Facility Name
Service de Chirurgie Digestive,Institut de Cancérologie de Lorraine
City
Nancy
Country
France
Facility Name
Service de Chirurgie Digestive, Hôtel Dieu - CHU de Nantes
City
Nantes
Country
France
Facility Name
Service de Chirurgie Digestive, CHU Carémeau - Nîmes
City
Nîmes
Country
France
Facility Name
GH Paris Saint Joseph
City
Paris
Country
France
Facility Name
Service de Chirurgie Digestive et Oncologique, Hôpital Bicêtre - APHP
City
Paris
Country
France
Facility Name
Service de Chirurgie Digestive, Hôpital les Diaconnesses
City
Paris
Country
France
Facility Name
Service de Chirurgie Digestive, Hôpital Saint-Antoine - APHP
City
Paris
Country
France
Facility Name
Service de Chirurgie Digestive, Hôpital Saint-Louis - APHP Paris
City
Paris
Country
France
Facility Name
Service de Chirurgie Digestive, Hôpital Pontchaillou - CHU Rennes
City
Rennes
Country
France
Facility Name
Service de Chirurgie Digestive, Hôpital Charles Nicolle - CHU de Rouen
City
Rouen
Country
France
Facility Name
Service de Chirurgie Digestive, Hôpital Purpan - CHU de Toulouse
City
Toulouse
Country
France
Facility Name
Service de chirurgie digestive, CHRU de Nancy -Hôpital de Brabois
City
Vandœuvre-lès-Nancy
Country
France
Facility Name
Département de chirurgie digestive, Institut Gustave Roussy
City
Villejuif
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Optimisation of Response for Organ Preservation in Rectal Cancer : Neoadjuvant Chemotherapy and Radiochemotherapy vs. Radiochemotherapy

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