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NCT Number: NCT02514278

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

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Service de Chirurgie Digestive, CHU Amiens Picardie, Amiens, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Neoadjuvant chemotherapy Folfirinox, 4 cycles

Drug
  • 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

50 Gy, 2 Gy/session; 25 fractions

Radiation

Radiochemotherapy 5 weeks

Local excision in good responders

Procedure

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.

Rectal excision in bad responders

Procedure

Capecitabine

Drug

1600 mg/m2 daily 5 days/7

Primary outcomes

  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 outcomes

  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 (radiomic analysis) 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

Sponsors and collaborators

Lead sponsor

University Hospital, Bordeaux

Other

Registry information

Acronym: GRECCAR12

Important dates

Study start
2016
Primary completion
2022
Study completion
2024
First posted
Aug 3, 2015
Registry last updated
May 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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