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

Rectal Adenocarcinoma Clinical Trial

— GRECCAR8  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02314182
• Other study ID #: 2014.847
• Status: Completed
• Phase: Phase 3
• Start date: November 20, 2014
• Est. completion date: February 27, 2018

Study information

• Verified date: October 2019
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: February 27, 2018
• Est. primary completion date: February 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Rectal Adenocarcinoma

Intervention

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

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).

Locations

Country	Name	City	State
France	Service d'Oncologie Médicale, Clinique du Cap-d'Or	La Seyne-sur-Mer
France	Service de Chirurgie Générale et Digestive, CHRU Claude Huriez	Lille
France	Service de Chirurgie Générale et Digestive, Centre hospitalier Lyon Sud, HCL	Pierre Benite

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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