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

NCT02314182 | Completed Phase 3 DMC

• 1 other identifier: 2014.847
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Rectal Adenocarcinoma

Keywords

Rectal adenocarcinoma; unresectable; surgery; chemotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Progression free survival

  up to 2 years

• Quality of life

  Up to 2 years

• Toxicity of chemotherapy (Common Toxicity Criteria for Adverse Events (NCI-CTC-AE V4.0)

  Up to 2 years

• Response of the metastatic disease to systemic chemotherapy (RECIST 1.1 criteria)

  up to2 years

• Time to disease progression

  up to 2 years

Study Arms (2)

A Primary tumor resection + chemotherapy

EXPERIMENTAL

PT resection + systemic chemotherapy +/- target therapy

Procedure: Primary tumor resection + chemotherapy

B Oxaliplatin/irinotecan + capecitabine, 5-FUI ± bevacizumab

OTHER

Chemotherapy (+/- target therapy)

Drug: Oxaliplatin/irinotecan + capecitabine, 5-FUI ± bevacizumab

Interventions

Primary tumor resection + chemotherapy PROCEDURE

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

A Primary tumor resection + chemotherapy

Oxaliplatin/irinotecan + capecitabine, 5-FUI ± bevacizumab DRUG

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).

Also known as: EGFR antibodies panitumumad and cetuxiamb in case of KRAS wild-type tumors.

B Oxaliplatin/irinotecan + capecitabine, 5-FUI ± bevacizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (3)

Service de Chirurgie Générale et Digestive, Centre hospitalier Lyon Sud, HCL

Pierre-Bénite, France, 69495, France

Location

Service d'Oncologie Médicale, Clinique du Cap-d'Or

La Seyne-sur-Mer, 83500, France

Location

Service de Chirurgie Générale et Digestive, CHRU Claude Huriez

Lille, 59067, France

Location

Related Publications (1)

• 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.

  PMID: 25849254 RESULT

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Drug Therapy; Oxaliplatin; Irinotecan; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Eddy COTTE

  Service de Chirurgie Générale et Digestive, Centre hospitalier Lyon Sud, HCL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2014
• First Posted: December 11, 2014
• Study Start: November 20, 2014
• Primary Completion: February 1, 2018
• Study Completion: February 27, 2018
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

FR (3)