on inferiority study of preoperative chemotherapy without pelvic irradiation for rectal cancer
- Conditions
- Adults = 18 years with middle or low locally advanced resectable rectal carcinomaMedDRA version: 20.0Level: PTClassification code 10038038Term: Rectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-002717-35-FR
- Lead Sponsor
- ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS (AP-HP)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 574
- 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
- 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 <2x109/L and/or platelet count <100x109/L), peripheral neuropathy with permanent invalidity before treatment initiation
- severe renal insufficiency (Creatinin clearance <30 ml/min)
- contraindications to folinic acid : Biermer anemia and other anemia related to B12 vitamin insufficiency
- contraindications to capecitabin : severe renal insufficiency (Creatinin clearance <30 ml/min)
- live attenuated vaccine should not be used during and 6 months after preoperative treatment.
- Previous colorectal cancer
- Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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:<br>1. acute and late treatment related toxicity<br>2. compliance to treatment<br>3. radiological response<br>4. R0 resection rate and quality of total mesorectal excision<br>5. sphincter saving surgery rate<br>6. postoperative morbidity and mortality<br>7 pathologic response after chemotherapy and chemoradiotherapy <br>8. loco-regional recurrence free survival<br>9. uncontrolled local recurrence<br>10. overall survival<br>11. bowel function<br>12. sexual function<br>13. quality of life – physical functioning<br>;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 Outcome Measures
Name Time Method