GRECCAR 8: Primary Tumor Resection in Rectal Cancer With Unresectable Metastasis (GRECCAR8)

GRECCAR 8 : Impact on Survival of the Primary Tumor Resection in Rectal Cancer With Unresectable Synchronous Metastasis a Randomized Multicenter Study

A prospective, open, multicenter, randomized III trial with two arms:

• Arm A: Primary tumor resection , followed by chemotherapy
• Arm B: Chemotherapy alone. Compare overall 2-year survival rates in patients treated for resectable rectal adenocarcinoma with unresectable metastasis, treated either with the primary tumor resection with chemotherapy +/- target therapy, or with chemotherapy (+/- target therapy) alone.

Study Overview

• Status: Completed
• Conditions: Rectal Adenocarcinoma
• Intervention / Treatment: Procedure: Primary tumor resection + chemotherapy; Drug: Oxaliplatin/irinotecan + capecitabine, 5-FUI ± bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • La Seyne-sur-Mer, France, 83500
    • Service d'Oncologie Médicale, Clinique du Cap-d'Or
  • Lille, France, 59067
    • Service de Chirurgie Générale et Digestive, CHRU Claude Huriez
  • France
    • Pierre-Bénite, France, France, 69495
      • Service de Chirurgie Générale et Digestive, Centre hospitalier Lyon Sud, HCL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Non-complicated primary tumor (i.e. tumor without obstruction, bleeding, abscess or perforation requiring emergency surgery and/or contra-indicating first-line chemotherapy)
• Unresectable synchronous metastases
• ECOG performance status 0-1
• Rectal adenocarcinoma (<15 cm from the anal verge) with few or no symptoms and unresectable metastasis (assessed by the investigator) unsuitable for curative treatment
• No known unresectable primary tumor (with clear margin >1mm) on CT-scan and MRI
• No disease progression under chemotherapy (for at least 4 cycles);
• Assessment of KRAS status before randomization (wild type or mutated);
• Life expectancy without cancer >2 years
• White blood cell count ≥ 3 x 109/L, with neutrophils ≥ 1,5 x 109/L, platelet count ≥ 100 x 109/L, hemoglobin°≥ 9 g/dL (5,6 mmol/l)
• Total bilirubin ≤ 1.5 x ULN (upper limit of normal), ASAT and ALAT ≤ 2.5 x ULN, alkaline phosphatase°≤°1.5°x ULN, serum creatinine ≤ 1.5 x ULN;
• Age ≥ 18 years ≤ 75 years
• Patients with childbearing potential should use effective contraception during the study and up 6 months after the end of chemotherapy
• Covered by a Health System where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research;
• Signed written informed consent obtained prior to any study-specific screening procedures

Exclusion Criteria:

• Rectal tumor operated before inclusion
• Symptoms related to the rectal tumor requiring first intention rectal surgery (appreciated by investigator)
• Contra-indication for surgery
• Resectable metastases
• Complicated (obstruction, bleeding, abscess, perforation) primary tumor requiring emergency surgery and/or contra-indicating first line-chemotherapy
• Non-resectable primary tumor (with wild margin)
• Age > 75 years < 18 years
• ECOG performance status > 2
• Under nutrition (albumin < 30 g/l)
• Peritoneal carcinomatosis
• Disease progression under chemotherapy (RECIST 1.1 criteria)
• Known hypersensitivity reaction or specific contraindications to any of the components of study treatments
• Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia
• Pregnancy (absence to be confirmed by ß-hCG test) or breast-feeding;
• Previous malignancy in the last 5 years
• Medical, geographical, sociological, psychological or legal conditions that would prevent the patient from completing the study or signing the informed consent; in the investigator's opinion
• Any significant disease which, in the investigator's opinion, excludes the patient from the study
• Under an administrative or legal supervision.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A Primary tumor resection + chemotherapy; PT resection + systemic chemotherapy +/- target therapy	Procedure: Primary tumor resection + chemotherapy; Step 1: Primary Tumor (PT) resection; Within 3 weeks after randomization; Immunonutrition given 7 days prior to PT resection; Mechanical bowel preparation performed before surgery according to the local practices; Performed by laparoscopy (recommended) or by laparotomy (at the investigator's discretion) Step 2: postoperative CT-scan; Must be performed within 4 weeks after surgery; CT-scan/MRI with the same criteria as pre-treatment evaluation Step 3: Chemotherapy +/- target therapy; Within 4 weeks after the surgery; Chemotherapy administered according to the usual scheme for the chosen protocol; All validated and/or registered perioperative rectal cancer treatments authorized; The duration of one treatment cycle depending on the type of treatment administered; Radiotherapy is allowed after randomization if indicated
Other: B Oxaliplatin/irinotecan + capecitabine, 5-FUI ± bevacizumab; Chemotherapy (+/- target therapy)	Drug: Oxaliplatin/irinotecan + capecitabine, 5-FUI ± bevacizumab; Treatment will start within 3 weeks after randomization; Chemotherapy will be administered according to the regimen in the chosen protocol and validated by the MDOC of each center. If complications occur, emergency surgery can be performed according to the local practices of each investigator center. Radiotherapy is allowed after randomization if indicated (MDOC).; Other Names: EGFR antibodies panitumumad and cetuxiamb in case of KRAS wild-type tumors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival, defined as the time interval between the date of randomization and the date of death, with a 24 months' follow-up, in both treatment arms.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression free survival will be assessed every 3 months during follow-up and will be estimated at 24 months.	up to 2 years
Quality of life	Quality of life will be assessed at the time of randomization and then every 3 months in both treatment arms. The EORTC QLQ-C30, QLQ-CR29 questionnaires will be used.	Up to 2 years
Toxicity of chemotherapy (Common Toxicity Criteria for Adverse Events (NCI-CTC-AE V4.0)	Chemotherapy toxicity will be graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTC-AE V4.0) in both treatment arms	Up to 2 years
Response of the metastatic disease to systemic chemotherapy (RECIST 1.1 criteria)	The response rate of the metastatic disease will be evaluated in both treatment arms by CT scan and analyzed using the RECIST 1.1 criteria	up to2 years
Time to disease progression	Time to disease progression is defined as the lapse of time between the date of randomization and the first date of progression (clinical or imaging) of the metastatic disease in both treatment arms, or of the primary rectal tumor in the chemotherapy arm (Arm B)	up to 2 years
Post-operative morbidity	The evaluation of post-operative morbidity and mortality will be assessed in the primary tumor resection arm (Arm A) and in the chemotherapy arm (Arm B) for patients who require emergency surgery. The post-operative complications will be evaluated according to the Clavien-Dindo Classification of Surgical Complication and graded 0 to V.	within 30 days after surgical intervention

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Eddy COTTE, Service de Chirurgie Générale et Digestive, Centre hospitalier Lyon Sud, HCL

Publications and helpful links

General Publications

• Cotte E, Villeneuve L, Passot G, Boschetti G, Bin-Dorel S, Francois Y, Glehen O; French Research Group of Rectal Cancer Surgery (GRECCAR). GRECCAR 8: impact on survival of the primary tumor resection in rectal cancer with unresectable synchronous metastasis: a randomized multicentre study. BMC Cancer. 2015 Feb 12;15:47. doi: 10.1186/s12885-015-1060-0.

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2014
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): February 27, 2018

Study Registration Dates

• First Submitted: November 12, 2014
• First Submitted That Met QC Criteria: December 10, 2014
• First Posted (Estimated): December 11, 2014

Study Record Updates

• Last Update Posted (Estimated): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: chemotherapy; surgery; unresectable; Rectal adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; Irinotecan; Drug Therapy
• Other Study ID Numbers: 2014.847