Clinical trial NCT02314182: GRECCAR 8: Primary Tumor Resection in Rectal Cancer With Unresectable Metastasis
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rectal Adenocarcinoma
Keywords: Rectal adenocarcinoma
unresectable
surgery
chemotherapy
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2014-12-11
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: Overall survival
timeFrame: up to 2 years
Secondary outcomes:
measure: Progression free survival
timeFrame: up to 2 years
measure: Quality of life
timeFrame: Up to 2 years
measure: Toxicity of chemotherapy (Common Toxicity Criteria for Adverse Events (NCI-CTC-AE V4.0)
timeFrame: Up to 2 years
measure: Response of the metastatic disease to systemic chemotherapy (RECIST 1.1 criteria)
timeFrame: up to2 years
measure: Time to disease progression
timeFrame: up to 2 years
measure: Post-operative morbidity
timeFrame: within 30 days after surgical intervention
Other outcomes:
Locations:
city: La Seyne-sur-Mer
country: France
facility: Service d'Oncologie Médicale, Clinique du Cap-d'Or
city: Lille
country: France
facility: Service de Chirurgie Générale et Digestive, CHRU Claude Huriez
city: Pierre Benite
country: France
facility: Service de Chirurgie Générale et Digestive, Centre hospitalier Lyon Sud, HCL
Study officials:
affiliation: Service de Chirurgie Générale et Digestive, Centre hospitalier Lyon Sud, HCL
name: Eddy COTTE
role: PRINCIPAL_INVESTIGATOR
References:
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.