Clinical trial NCT02514278: Optimisation of Response for Organ Preservation in Rectal Cancer : Neoadjuvant Chemotherapy and Radiochemotherapy vs. Radiochemotherapy
Official title: Optimisation of Response for Organ Preservation in Rectal Cancer : Neoadjuvant Chemotherapy and Radiochemotherapy vs. Radiochemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rectal Cancer
Keywords: Organ preservation
Local excision
Radiochemotherapy
Neoadjuvant chemotherapy
Folfirinox
Tumour response
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2015-08-03
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Standard treatment of rectal cancer is rectal excision with neoadjuvant radiochemotherapy. A new concept suggests organ preservation as an alternative to rectal excision in good responders after neoadjuvant radiochemotherapy to decrease surgical morbidity and increase quality of life. The rational is the fact that 15% of patients have sterilized tumours after radiochemotherapy for T3T4 rectal cancer. The French GRECCAR 2 trial is the first phase III trial investigating this strategy: patients with T2T3 low rectal carcinomas (size ≤4 cm) received 50 Gy with capecitabine and good clinical responders (≤2 cm) were randomized between local and rectal excision. The main findings were: the rate of complete pathologic response was higher after radiochemotherapy for small T2T3 than for T3T4 tumours (40% vs 15% ypT0) and good pathologic responders (ypT0-1) were associated with zero positive mesorectal nodes.

The objective of the new trial is to increase the proportion of patients treated with organ preservation by optimizing tumour response. As compared to Folfiri, tritherapy Folfirinox has been shown to enhance the response rate. In patients with colorectal metastases, response rate and R0 resection were twice higher, resulting in improved survival. Folfirinox also increases response and chance of R0 resection rates in initially unresectable colorectal metastases, compared to standard or intensified bi-chemotherapy regimens. Adding two months of neoadjuvant chemotherapy (Folfirinox) before radiochemotherapy, the investigators expect to increase chance of organ preservation rate, as compared to radiochemotherapy alone.


Eligibility criteria: Inclusion Criteria:

* Rectal adenocarcinoma
* cT2T3
* cN0-1 (≤ 3 positive lymph nodes or size ≤8mm)
* Tumour size ≤4 cm
* Location ≤10 cm from the anal verge
* No distant metastasis
* Patient ≥18 years
* ECOG ≤2
* Effective contraception during the study
* Patient and doctor have signed informed consent

Exclusion Criteria:

* T1 or T4
* Tumour size \>4cm
* N2 (\>3 positive lymph nodes or size \>8mm)
* Tumour \> 10 cm from the anal verge
* Distant metastasis
* Chronic intestinal inflammation and/or bowel obstruction
* Contra indication for chemotherapy and/or radiotherapy
* Previous pelvic radiotherapy or chemotherapy
* Severe renal, hepatic insufficiency (serum creatinine\<30ml/min)
* Peripheral neuropathy \> grade 1
* Complete or partial Dihydropyrimidine deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)
* Concomitant treatment with millepertuis, yellow fever vaccine, phenytoin or sorivudine (or chemically equivalent)
* Pregnant or breast-feeding woman.
* Persons deprived of liberty or under guardianship
* Impossibility for compliance to follow-up

Primary outcomes:
measure: Rate of organ preservation and absence of stoma
timeFrame: 1 year after surgery
Secondary outcomes:
measure: Compliance to treatment
timeFrame: From beginning of neoadjuvant treatment until surgery, expected average 20 weeks after neoadjuvant treatment
measure: Tolerance to treatment
timeFrame: From beginning of neoadjuvant treatment until 1 year after surgery
measure: Rate of clinical complete response
timeFrame: At 8 weeks after neoadjuvant treatment
measure: Rate of radiological response
timeFrame: At 8 weeks after neoadjuvant treatment
measure: Rate of complete pathologic response
timeFrame: At surgery, expected average 10 weeks after neoadjuvant treatment
measure: Correlation between radiological and clinical response
timeFrame: Between 8 to 10 weeks after neoadjuvant treatment
measure: Correlation between radiological (radiomic analysis) and pathologic response
timeFrame: Between 8 to 10 weeks after neoadjuvant treatment
measure: Rate of curative surgery
timeFrame: At surgery, expected average 10 weeks after neoadjuvant treatment
measure: Surgical morbidity
timeFrame: From surgery until 1 year of follow-up
measure: Quality of life
timeFrame: From randomization until 1 year after surgery
measure: Local recurrence
timeFrame: From surgery until 3 years of follow-up
measure: Overall survival
timeFrame: From surgery until 3 years of follow-up
measure: Disease-free survival
timeFrame: From surgery until 3 years of follow-up
Other outcomes:
Locations:
city: Amiens
country: France
facility: Service de Chirurgie Digestive, CHU Amiens Picardie
city: Besançon
country: France
facility: Service de Chirurgie Digestive, CHU de Besançon
city: Bordeaux
country: France
facility: Service de Chirurgie Digestive, Hôpital Haut-Lévêque - CHU de Bordeaux
city: Bordeaux
country: France
facility: Service de Chirurgie Digestive, Institut Bergonié
city: Clermont-Ferrand
country: France
facility: Service de Chirurgie Digestive, CHU Estaing - CHRU Clermont Ferrand
city: Clichy
country: France
facility: Service de Chirurgie Digestive, Hôpital Beaujon - APHP
city: Dijon
country: France
facility: Service de Chirurgie Digestive, Centre Georges François Leclerc - Dijon
city: La Tronche
country: France
facility: Service de Chirurgie Digestive, Hôpital Albert Michallon - CHU de Grenoble
city: Lille
country: France
facility: Service de Chirurgie Digestive, Centre Oscar Lambret - Lille
city: Lyon
country: France
facility: Service de Chirurgie Digestive, Centre Léon Bérard - Lyon
city: Lyon
country: France
facility: Service de Chirurgie Digestive, Hôpital Lyon Sud - CHU Lyon
city: Marseille
country: France
facility: Service de Chirurgie Digestive, CHU de la Timone - Marseille
city: Marseille
country: France
facility: Service de Chirurgie Digestive, Institut Paoli Calmette - Marseille
city: Marseille
country: France
facility: Service de Chirurgie Digestives, Hôpital Européen de Marseille
city: Montpellier
country: France
facility: Service de Chirurgie Digestive, Institut du Cancer de Montpellier
city: Mougins
country: France
facility: Service d'Oncologie et Radiothérapie, Centre Azuréen de Cancérologie
city: Nancy
country: France
facility: Service de Chirurgie Digestive,Institut de Cancérologie de Lorraine
city: Nantes
country: France
facility: Service de Chirurgie Digestive, Hôtel Dieu - CHU de Nantes
city: Nîmes
country: France
facility: Service de Chirurgie Digestive, CHU Carémeau - Nîmes
city: Paris
country: France
facility: GH Paris Saint Joseph
city: Paris
country: France
facility: Service de Chirurgie Digestive et Oncologique, Hôpital Bicêtre - APHP
city: Paris
country: France
facility: Service de Chirurgie Digestive, Hôpital les Diaconnesses
city: Paris
country: France
facility: Service de Chirurgie Digestive, Hôpital Saint-Antoine - APHP
city: Paris
country: France
facility: Service de Chirurgie Digestive, Hôpital Saint-Louis - APHP Paris
city: Rennes
country: France
facility: Service de Chirurgie Digestive, Hôpital Pontchaillou - CHU Rennes
city: Rouen
country: France
facility: Service de Chirurgie Digestive, Hôpital Charles Nicolle - CHU de Rouen
city: Toulouse
country: France
facility: Service de Chirurgie Digestive, Hôpital Purpan - CHU de Toulouse
city: Vandœuvre-lès-Nancy
country: France
facility: Service de chirurgie digestive, CHRU de Nancy -Hôpital de Brabois
city: Villejuif
country: France
facility: Département de chirurgie digestive, Institut Gustave Roussy
Study officials:
affiliation: University Hospital Bordeaux, France
name: Christophe LAURENT, Prof.
role: PRINCIPAL_INVESTIGATOR
References: