Multicenter Randomized Phase III Trial Evaluating Contact X-ray Brachytherapy for Rectal Preservation in Intermediate Substage Rectal Adenocarcinoma
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Adult With Intermediate Low or Mid Rectal Adenocarcinoma
- Sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Enrollment
- 212
- Locations
- 11
- Primary Endpoint
- Survival with organ preservation
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
Indication : Adult patients with intermediate low or mid rectal adenocarcinoma to be treated with total neoadjuvant therapy (TNT) potentially eligible for rectal preservation.
Primary objective is to assess efficacy of contact X-ray brachytherapy (CXB) in addition to TNT in order to increase survival with organ preservation (OP), in selected intermediate risk group of rectal adenocarcinomas (size from 3.1 to 6 cm, cT2N1 or T3N0-1, M0).
Detailed Description
It is an open label phase III randomized controlled clinical trial comparing 2 arms: * Control arm A consists in TNT regimen, with an induction chemotherapy Modified FOLFIRINOX (mFOLFIRINOX) 6 cycles over 12 weeks, followed by nCRT 50 Gy over 5 weeks with concomitant capecitabine (CAP50 Gy). * Experimental arm B consists in addition of three fractions of CXB every two weeks between end of mFOLFIRINOX and nCRT. Clinical, endoscopic and radiological evaluation will be performed 7 weeks after the end of nCRT in both arms: * In case of cCR, local excision or surveillance will be proposed to patients regarding center choice * In the absence of cCR patients will be treated by TME, followed by adjuvant chemotherapy (mFOLFOX 6 cycles or capecitabine 3 cycles over 12 weeks).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient with histologically proven rectal adenocarcinoma
- •Intermediate risk factors: size ≥ 3.1 cm and ≤ 6 cm, \< 66% circumference, cT2N1 or T3N0-1, M0 at diagnostic.
- •Accessible by digital rectal exam, distal or middle rectum (\<11 cm from anal verge), not significantly involving the anal canal (external sphincter not involved) at diagnostic.
- •Operable patient
- •Patient who is about to start mFolfirinox chemotherapy. The registration is possible before, during or at the end of 4 cycles of mFolfirinox chemotherapy
- •Age ≥ 18 years
- •WHO status 0 or 1 at diagnosis
- •Biological values within the following limits: Total Bilirubin ≤ 1.5 times the upper limit of normal (ULN); ASAT and ALAT ≤ 5 N; Creatinine ≤ 1.5 N and creatinine clearance\> 60 ml/min; Neutrophils ≥ 1.
- •109 / L; Platelets ≥
- •109 / L; Hemoglobin ≥ 9 g / dL (patients can be included even if they have been transfused); Albuminemia≥30g / L before starting mFolfirinox chemotherapy;
Exclusion Criteria
- •Other cancer in the 5 years prior to start m Folfirinox chemotherapy or concomitant (except in situ cancer of the cervix, or basal cell carcinoma of the skin).
- •History of pelvic irradiation or pelvis surgery
- •Early tumor (T1-2N0, size \< 3.1 cm) or advanced tumor (T3 \> 6cm of circumference, T4, N2, M1) at diagnostic
- •Patient who stopped mFolfirinox after 3 cycles or less
- •Dihydropyrimidine dehydrogenase (DPD) deficiency. The blood uracil level must be measured at screening. The uracilemia dosing result is mandatory prior the inclusion of patient.
- •Given the oxaliplatin-related risk of prolongation of QT, patient with hypokalemia less than normal, hypomagnesemia, hypocalcemia, and QT/QTc interval longer than 450 msec for men and longer than 470 msec for women on the inclusion ECG should not be allowed at diagnostic.
- •Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last 3 months, significant arrhythmia).
- •Unbalanced serious illness, underlying infection likely to prevent the patient from receiving treatment current pregnancy (obligatory pregnancy test at baseline) or breastfeeding.
- •Psychiatric illness compromising the understanding of information or the conduct of the study.
- •Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent.
Outcomes
Primary Outcomes
Survival with organ preservation
Time Frame: at the end of the study,15 months after the first inclusion
defined as a rectum intact, owing to: * no radical TME, * no locoregional regrowth unless amenable to limited curative (R0) salvage surgery by local excision (LE), and no permanent stoma (including a never reversed protective stoma, or a stoma owing to toxicities and/or poor functional outcomes).