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

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ClinicalTrials.gov Identifier: NCT02514278
Recruitment Status : Active, not recruiting
First Posted : August 3, 2015
Last Update Posted : July 6, 2022
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux

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.


Condition or disease Intervention/treatment Phase
Rectal Cancer 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 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 218 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Optimisation of Response for Organ Preservation in Rectal Cancer : Neoadjuvant Chemotherapy and Radiochemotherapy vs. Radiochemotherapy
Actual Study Start Date : January 28, 2016
Actual Primary Completion Date : June 9, 2022
Estimated Study Completion Date : January 2024

Arm Intervention/treatment
Experimental: Chemotherapy and Radiochemotherapy

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)

Drug: 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

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

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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. Tolerance to treatment [ Time Frame: From beginning of neoadjuvant treatment until 1 year after surgery ]
    Number of patients with adverse events

  3. 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

  4. 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

  5. Rate of complete pathologic response [ Time Frame: At surgery, expected average 10 weeks after neoadjuvant treatment ]
    To determine the rate of ypT0

  6. 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)

  7. 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)

  8. Rate of curative surgery [ Time Frame: At surgery, expected average 10 weeks after neoadjuvant treatment ]
    To determine the rate of R0 resection

  9. Surgical morbidity [ Time Frame: From surgery until 1 year of follow-up ]
    To analyse the cumulative Clavien-Dindo at 1 year

  10. Quality of life [ Time Frame: From randomization until 1 year after surgery ]
    To examine score of questionnaires : QLQ CR-30, QLQ CR-29

  11. Local recurrence [ Time Frame: From surgery until 3 years of follow-up ]
    To determine the rate of local recurrence at 3 years

  12. Overall survival [ Time Frame: From surgery until 3 years of follow-up ]
    To determine the rate of overall survival at 3 years

  13. Disease-free survival [ Time Frame: From surgery until 3 years of follow-up ]
    To determine the rate of disease-free survival at 3 years



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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:

  • 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

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): NCT02514278


Locations
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Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
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Principal Investigator: Eric RULLIER, Prof. University Hospital Bordeaux, France
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Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT02514278    
Other Study ID Numbers: CHUBX 2014/33
First Posted: August 3, 2015    Key Record Dates
Last Update Posted: July 6, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University Hospital, Bordeaux:
Organ preservation
Local excision
Radiochemotherapy
Neoadjuvant chemotherapy
Folfirinox
Tumour response
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Folfirinox
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents