Informations générales (source: ClinicalTrials.gov)
Non Inferiority Multicenter Phase III Randomized Trial Comparing Preoperative Chemotherapy Only to Chemotherapy Followed by Chemoradiotherapy for Locally Advanced Resectable Rectal Cancer (Intergroup FRENCH-GRECCAR- PRODIGE)
Interventional
Phase 3
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
juin 2019
décembre 2026
11 septembre 2025
This study is a non-inferiority phase III randomised trial comparing preoperative
chemotherapy alone (modified FOLFIRINOX) to chemotherapy followed by chemoradiotherapy in
patients with primary resectable locally advanced rectal cancer. The primary endpoint of
the study is 3-year progression free survival.
Expected 3 year PFS rate in the preoperative chemotherapy followed by chemoradiotherapy
arm is 75%. This hazard rate, in an exponential survival model, corresponds to a decrease
in the 3-year PFS rate on the preoperative chemotherapy arm to 67%. The study will
randomize 540 patients (270 in the chemotherapy group and 270 in the chemoradiotherapy
group) in 42 french academic centers.
Etablissements
Critères
Tous
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.
- 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.
- 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.
- Recent or concomitant treatment with brivudine is contraindicated
- 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), complete and permanent insufficiency in dihydropyrimidine dehydrogenase
- 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.