Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    GRECCAR12
Previous Study | Return to List | Next Study

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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02514278
Recruitment Status : Recruiting
First Posted : August 3, 2015
Last Update Posted : January 10, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux

Tracking Information
First Submitted Date  ICMJE July 6, 2015
First Posted Date  ICMJE August 3, 2015
Last Update Posted Date January 10, 2019
Actual Study Start Date  ICMJE January 28, 2016
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 31, 2015)
Rate of organ preservation and absence of stoma [ Time Frame: 1 year after surgery ]
Number of patients with organ preservation and absence of stoma at 1 year after surgery
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02514278 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2015)
  • Compliance to treatment [ Time Frame: From beginning of neoadjuvant treatment until surgery, expected average 20 weeks after neoadjuvant treatment ]
    Number of patients receiving full neoadjuvent treatment and the allocated surgery
  • Tolerance to treatment [ Time Frame: From beginning of neoadjuvant treatment until 1 year after surgery ]
    Number of patients with adverse events
  • Rate of clinical complete response [ Time Frame: At 8 weeks after neoadjuvant treatment ]
    To determine the rate of grade 1 : no tumor at digital examination
  • Rate of radiological response [ Time Frame: At 8 weeks after neoadjuvant treatment ]
    To determine the rate of tumor ≤ 2 cm with TRG1-3 at MRI
  • Rate of complete pathologic response [ Time Frame: At surgery, expected average 10 weeks after neoadjuvant treatment ]
    To determine the rate of ypT0
  • Correlation between radiological and clinical response [ Time Frame: Between 8 to 10 weeks after neoadjuvant treatment ]
    To analyse the correlation between radiological response ( tumor ≤ 2 cm with TRG1-3 at MRI) and clinical response (grade 1)
  • Correlation between radiological and pathologic response [ Time Frame: Between 8 to 10 weeks after neoadjuvant treatment ]
    To analyse the correlation between radiological response ( tumor ≤ 2 cm with TRG1-3 at MRI) and pathological response (ypT0)
  • Rate of curative surgery [ Time Frame: At surgery, expected average 10 weeks after neoadjuvant treatment ]
    To determine the rate of R0 resection
  • Surgical morbidity [ Time Frame: From surgery until 1 year of follow-up ]
    To analyse the cumulative Clavien-Dindo at 1 year
  • Quality of life [ Time Frame: From randomization until 1 year after surgery ]
    To examine score of questionnaires : QLQ CR-30, QLQ CR-29
  • Local recurrence [ Time Frame: From surgery until 3 years of follow-up ]
    To determine the rate of local recurrence at 3 years
  • Overall survival [ Time Frame: From surgery until 3 years of follow-up ]
    To determine the rate of overall survival at 3 years
  • Disease-free survival [ Time Frame: From surgery until 3 years of follow-up ]
    To determine the rate of disease-free survival at 3 years
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Optimisation of Response for Organ Preservation in Rectal Cancer : Neoadjuvant Chemotherapy and Radiochemotherapy vs. Radiochemotherapy
Official Title  ICMJE Optimisation of Response for Organ Preservation in Rectal Cancer : Neoadjuvant Chemotherapy and Radiochemotherapy vs. Radiochemotherapy
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE Rectal Cancer
Intervention  ICMJE
  • Drug: Neoadjuvant chemotherapy Folfirinox, 4 cycles
    • oxaliplatin: 85 mg/m2
    • irinotecan: 180 mg/m²
    • folinic acid: 400 mg/m2
    • 5FU: 2400 mg/m2
  • Radiation: 50 Gy, 2 Gy/session; 25 fractions
    Radiochemotherapy 5 weeks
  • Procedure: Local excision in good responders

    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.
  • Procedure: Rectal excision in bad responders
  • Drug: Capecitabine
    1600 mg/m2 daily 5 days/7
Study Arms  ICMJE
  • Experimental: Chemotherapy and Radiochemotherapy

    Neoadjuvant chemotherapy Folfirinox, 4 cycles:

    • oxaliplatin: 85 mg/m2
    • irinotecan: 180 mg/m²
    • folinic acid: 400 mg/m2
    • 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)

    Interventions:
    • Drug: Neoadjuvant chemotherapy Folfirinox, 4 cycles
    • Radiation: 50 Gy, 2 Gy/session; 25 fractions
    • Procedure: Local excision in good responders
    • Procedure: Rectal excision in bad responders
    • Drug: Capecitabine
  • Active Comparator: Radiochemotherapy
    Radiochemotherapy: 5 weeks (50 Gy, 2 Gy/session ; 25 fractions) + capecitabine (1600 mg/m2 daily 5 days/7, excluding weekends)
    Interventions:
    • Radiation: 50 Gy, 2 Gy/session; 25 fractions
    • Procedure: Local excision in good responders
    • Procedure: Rectal excision in bad responders
    • Drug: Capecitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 31, 2015)
218
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Rectal adenocarcinoma
  • cT2T3
  • cN0-1 (≤ 3 lymph nodes, 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 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
  • Dihydropyrimidine dehydrogenase deficiency
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Eric RULLIER, Prof. (0)5 56 79 58 10 ext +33 eric.rullier@chu-bordeaux.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02514278
Other Study ID Numbers  ICMJE CHUBX 2014/33
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Bordeaux
Study Sponsor  ICMJE University Hospital, Bordeaux
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Eric RULLIER, Prof. University Hospital Bordeaux, France
PRS Account University Hospital, Bordeaux
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP