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

Primary Purpose

Rectal Adenocarcinoma

Status

Completed

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

Primary tumor resection + chemotherapy

Oxaliplatin/irinotecan + capecitabine, 5-FUI ± bevacizumab

About this trial

This is an interventional other trial for Rectal Adenocarcinoma focused on measuring Rectal adenocarcinoma, unresectable, surgery, chemotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Service d'Oncologie Médicale, Clinique du Cap-d'Or
Service de Chirurgie Générale et Digestive, CHRU Claude Huriez
Service de Chirurgie Générale et Digestive, Centre hospitalier Lyon Sud, HCL

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

A Primary tumor resection + chemotherapy

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

Arm Description

PT resection + systemic chemotherapy +/- target therapy

Chemotherapy (+/- target therapy)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Progression free survival

Progression free survival will be assessed every 3 months during follow-up and will be estimated at 24 months.

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.

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

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

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)

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.

Full Information

NCT ID

NCT02314182

First Posted

November 12, 2014

Last Updated

October 31, 2019

Sponsor

Hospices Civils de Lyon

1. Study Identification

Unique Protocol Identification Number

NCT02314182

Brief Title

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

Acronym

GRECCAR8

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

November 20, 2014 (Actual)

Primary Completion Date

February 2018 (Actual)

Study Completion Date

February 27, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hospices Civils de Lyon

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rectal Adenocarcinoma

Keywords

Rectal adenocarcinoma, unresectable, surgery, chemotherapy

7. Study Design

Primary Purpose

Other

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A Primary tumor resection + chemotherapy

Arm Type

Experimental

Arm Description

PT resection + systemic chemotherapy +/- target therapy

Arm Title

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

Arm Type

Other

Arm Description

Chemotherapy (+/- target therapy)

Intervention Type

Procedure

Intervention Name(s)

Primary tumor resection + chemotherapy

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin/irinotecan + capecitabine, 5-FUI ± bevacizumab

Other Intervention Name(s)

EGFR antibodies panitumumad and cetuxiamb in case of KRAS wild-type tumors.

Intervention Description

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).

Primary Outcome Measure Information:

Title

Overall survival

Description

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.

Time Frame

up to 2 years

Secondary Outcome Measure Information:

Title

Progression free survival

Description

Progression free survival will be assessed every 3 months during follow-up and will be estimated at 24 months.

Time Frame

up to 2 years

Title

Quality of life

Description

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.

Time Frame

Up to 2 years

Title

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

Description

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

Time Frame

Up to 2 years

Title

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

Description

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

Time Frame

up to2 years

Title

Time to disease progression

Description

Time Frame

up to 2 years

Title

Post-operative morbidity

Description

Time Frame

within 30 days after surgical intervention

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Eddy COTTE

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

La Seyne-sur-Mer

ZIP/Postal Code

83500

Country

France

Facility Name

Service de Chirurgie Générale et Digestive, CHRU Claude Huriez

City

Lille

ZIP/Postal Code

59067

Country

France

Facility Name

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

City

Pierre Benite

ZIP/Postal Code

69495

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

25849254

Citation

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.

Results Reference

derived

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

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