Clinical trial NCT05868317: Induction Chemotherapy Followed by Short Course Radiotherapy in Rectal Cancer
Official title: Induction Chemotherapy With FOLFIRINOX ( 5 Fluorouracil, Oxaliplatine and Irinotecan) Followed by Short Course Radiotherapy in Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Rectal Cancer
Locally Advanced
Lead sponsor: Salah Azaïz Cancer Institute
Sponsor class: OTHER
First posted: 2023-05-22
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Single-arm phase II trial evaluating induction chemotherapy with FOLFIRINOXm followed by short course radiotherapy (RT) in locally advanced rectal carcinoma

Detailed description: Total neoadjuvant treatment (TNT) is currently the standard of care in the management of locally advanced rectal cancer since recent studies have shown improved pathological complete response and disease-free survival with this approach. However, survival benefits remain unproven.

Two strategies of TNT are validated so far : induction chemotherapy with FOLFIRINOX followed by long course radio-chemotherapy (RCT) or short course RT (5x5 Gy) followed by consolidation chemotherapy with CAPOX (capecitabine and oxaliplatin) or FOLFOX (5 FU and oxaliplatin) .

The objective of investigators is to evaluate pathological complete response with a new strategy of TNT consisting in induction chemotherapy with FOLFIRINOXm followed by short course RT and a delayed surgery.

Eligibility criteria: Inclusion Criteria:

* World Health Organization (WHO) performance status : 0 or 1
* Histologically proven rectal adenocarcinoma \< 10 cm from anal margin on rectoscopy
* clinically T3 (cT3) or clinically T4 (cT4) and/ or N+ non metastatic rectal cancer
* Neutrophil count \> 1500 e/mm3
* Platelet count \>100000
* Hemoglobin \> 10 g/dl ( transfusion allowed)
* Normal bilirubin level
* Creatinine clearance \> 50 ml/mn

Exclusion Criteria:

* Distant metastases
* History of chemotherapy or radiotherapy
* Grade 1 neuropathy
* Patient undergoing treatment for another cancer
* Active infection or severe comorbidities contraindicating chemotherapy

Primary outcomes:
measure: Pathologic complete response
timeFrame: 1 month after surgery
Secondary outcomes:
measure: Disease free survival
timeFrame: 3 years
measure: overall survival
timeFrame: 3 years
measure: objective response rate to induction chemotherapy
timeFrame: immediately after completion of 6 cycles of chemotherapy ( each cycle is 14 days)
Other outcomes:
Locations:
city: Tunis
country: Tunisia
facility: Amel Mezlini
Study officials:
affiliation: Salah Azaiez Institute of oncology
name: Feryel letaief ksontini, A/Prof
role: STUDY_DIRECTOR
affiliation: Salah Azaiez Institute
name: Amina Mokrani, A/Prof
role: STUDY_CHAIR
affiliation: Salah Azaiez Institute
name: Mouna Ayadi, A/Prof
role: STUDY_CHAIR
References:
citation: Fernandez-Martos C, Pericay C, Aparicio J, Salud A, Safont M, Massuti B, Vera R, Escudero P, Maurel J, Marcuello E, Mengual JL, Saigi E, Estevan R, Mira M, Polo S, Hernandez A, Gallen M, Arias F, Serra J, Alonso V. Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: Grupo cancer de recto 3 study. J Clin Oncol. 2010 Feb 10;28(5):859-65. doi: 10.1200/JCO.2009.25.8541. Epub 2010 Jan 11.
citation: Conroy T, Bosset JF, Etienne PL, Rio E, Francois E, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouche O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardiere C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 May;22(5):702-715. doi: 10.1016/S1470-2045(21)00079-6. Epub 2021 Apr 13.