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

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Completed

CT.gov ID

NCT02314182

Collaborator

(none)

Enrollment

Locations

Arms

39.3

Actual Duration (Months)

1.7

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Rectal Adenocarcinoma	Procedure: Primary tumor resection + chemotherapy Drug: Oxaliplatin/irinotecan + capecitabine, 5-FUI ± bevacizumab	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Nov 20, 2014

Actual Primary Completion Date :

Feb 1, 2018

Actual Study Completion Date :

Feb 27, 2018

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Overall survival [up to 2 years]
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 [up to 2 years]
Progression free survival will be assessed every 3 months during follow-up and will be estimated at 24 months.
Quality of life [Up to 2 years]
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) [Up to 2 years]
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) [up to2 years]
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 [up to 2 years]
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 [within 30 days after surgical intervention]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Service d'Oncologie Médicale, Clinique du Cap-d'Or	La Seyne-sur-Mer	France	83500
2	Service de Chirurgie Générale et Digestive, CHRU Claude Huriez	Lille	France	59067
3	Service de Chirurgie Générale et Digestive, Centre hospitalier Lyon Sud, HCL	Pierre Benite	France	69495