GRECCAR 8: Primary Tumor Resection in Rectal Cancer With Unresectable Metastasis
- Conditions
- Rectal Adenocarcinoma
- Interventions
- Procedure: Primary tumor resection + chemotherapyDrug: Oxaliplatin/irinotecan + capecitabine, 5-FUI ± bevacizumab
- Registration Number
- NCT02314182
- Lead Sponsor
- Hospices Civils de Lyon
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 5
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A Primary tumor resection + chemotherapy Primary tumor resection + chemotherapy PT resection + systemic chemotherapy +/- target therapy B Oxaliplatin/irinotecan + capecitabine, 5-FUI ± bevacizumab Oxaliplatin/irinotecan + capecitabine, 5-FUI ± bevacizumab Chemotherapy (+/- target therapy)
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.
Trial Locations
- Locations (3)
Service de Chirurgie Générale et Digestive, Centre hospitalier Lyon Sud, HCL
🇫🇷Pierre Benite, 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