Adults = 18 years with middle or low locally advanced resectable rectal carcinoma MedDRA version: 20.0 Level: PT Classification code 10038038 Term: Rectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: OXALIPLATINE
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: OXALIPLATIN
CAS Number: 61825-94-3
Product Name: irinotecan
Pharmaceutical Form: Solution fo
Sponsors
ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically proven middle or low rectal carcinoma, = 10 cm from the anal verge on MRI (sagittal slide) - cT3N0 and/or cT1-T3N+ on pretreatment imaging work up (pelvic contrast enhanced MRI and/or endorectal ultrasound), - Pretreatment predictive circumferential margin > 2mm on pretreatment imaging work up (pelvic contrast enhanced MRI) - Patients must be 18 years old or older - A World Health Organization (WHO/ECOG) performance status of 0 or 1 - Informed consent signed - Patients of childbearing / reproductive potential should use adequate birth control measures during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 459 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 115
Exclusion criteria
Exclusion criteria: - Rectal tumor > 10 cm from the anal verge on MRI (sagittal slide) - cT4 tumor on pretreatment imaging work up (pelvic contrast enhanced MRI and/or endorectal ultrasound) or involvement of external sphincter - Circumferential margin = 2 mm on pretreatment imaging work up (pelvic contrast enhanced MRI) - Metastatic disease - Prior pelvic irradiation or any contraindication to pelvic irradiation - Contraindication to oxaliplatin or irinotecan or 5FU based chemotherapy - Concomitant treatment with warfarin is contraindicated and warafarin must be replaced whenever possible to allow for inclusion. - contraindications to 5-FU: complete and permanent insufficiency in dihydropyrimidine dehydrogenase, bone marrow insufficiency, chronic and severe infection - contraindication to irinotecan : inflammatory bowel disease, bilirubin serum level > 3 times the upper limit of the normal rate, severe bone marrow insufficiency, WHO/ECOG performence status > 2, - Concomitant treatment with millepertuis. - contraindication to oxaliplatin : *bone marrow insufficiency before treatment initiation (neutrophil count 5 years - Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial - protected adults - Pregnancy or breastfeeding - Patient with no national health or universal plan affiliation coverage.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the non-inferiority of preoperative chemotherapy only compared to chemoradiotherapy on oncologic outcomes in locally advanced resectable low or middle rectal cancer (cT3N0 and/or cT1-T3N+).;Secondary Objective: To assess and to compare the both treatment groups regarding: 1. acute and late treatment related toxicity 2. compliance to treatment 3. radiological response 4. R0 resection rate and quality of total mesorectal excision 5. sphincter saving surgery rate 6. postoperative morbidity and mortality 7 pathologic response after chemotherapy and chemoradiotherapy 8. loco-regional recurrence free survival 9. uncontrolled local recurrence 10. overall survival 11. bowel function 12. sexual function 13. quality of life – physical functioning ;Primary end point(s): The main endpoint of this phase III study is 3-year progression-free survival from the time to randomization. ;Timepoint(s) of evaluation of this end point: 3 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To assess and compare in both groups 1. acute and late treatment related toxicity: the rates of treatment related toxicity grade II or more 2. compliance to treatment: the rate of patients that receive full dose treatment 3. radiological response: the rate of radiologic response on post-treatment MRI based on tumor size reduction and tumor regression grade (ymrTRG) 4. R0 resection rate and quality of total mesorectal excision: the rate of complete R0 resection and quality of carcinologic resection (quality of mesorectal excision based on Quirke’s grading system, number of lymph node harvested, size of longitudinal and circumferential margin). 5. sphincter saving surgery rate: the rate of surgery with intestinal continuity and anal sphincter preservation 6. postoperative morbidity and mortality: 30 day or in-hospital postoperative morbidity and mortality rates 7. pathologic response after chemotherapy and chemoradiotherapy: rate of major pathologic response base on Rodel Tumor Regression Grade 8. loco-regional recurrence free survival: 3-year locoregional recurrence free survival rates 9. uncontrolled local recurrence: 3-year uncontrolled local recurrence free survival rates 10. overall survival: 3 and 5 year overall survival rates 11. bowel function: EORTC QLQ-CR29 and LARS Scores at diagnosis, after preoperative treatment, 6 months and 1 year after surgery. 12. sexual function: EORTC QLQ-CR29 at diagnosis, after preoperative treatment, 6 months and 1 year after surgery. 13. quality of life – physical functioning: appropriate dimensions of the QLQ-C30 score at diagnosis, after preoperative treatment, 6 months and 1 year after surgery. ;Timepoint(s) of evaluation of this end point: post treatment, 6 months, 1 year, 3 years, 5 years. | — |
Countries
France
Contacts
Public ContactDRCI Hôpital St Louis
ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS (AP-HP)
Outcome results
None listed