Multicenter Phase 2 Trial: a Tailored Strategy for Locally Advanced Rectal Carcinoma

Locally Advanced Malignant Neoplasm Clinical Trial

— GRECCAR4  

Official title:

A Randomized Multicenter Phase 2 Study: a Tailored Strategy for Locally Advanced Rectal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01333709
• Other study ID #: GRECCAR 4
• Secondary ID: 2010-023546-73
• Status: Completed
• Phase: Phase 2
• First received: April 8, 2011
• Last updated: August 16, 2017
• Start date: May 2011
• Est. completion date: September 2014

Study information

• Verified date: August 2017
• Source: Institut du Cancer de Montpellier - Val d'Aurelle
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether the tailored management of locally advanced rectal carcinoma can improve the oncologic and functional outcome.

Description:

Locally advanced rectal carcinoma raise the issue of both the oncological control, local and general, and the therapeutic morbidity. Surgery alone can cure only one out of two patients, radiochemotherapy improves the local control but the metastatic risk remains about 30% with enhanced postoperative morbidity and poor functional results. The tumor response to preoperative treatment is the major prognostic factor which revealed the aggressiveness of the tumor. To this day, there are no biologic predictive markers for tumor response.

The purpose of this trial is to tailor the management according to the early tumoral response after short and intensive induction trichemotherapy. MRI volumetric tumor response will be used to distinguish between good responders and bad responders.

"Very good" responders will be randomized to either immediate surgery or radiochemotherapy followed by surgery (Standard arm: Cap 50). "Good or bad" responders will be randomized between two arms: intensive radiochemotherapy (Cap 60) or the standard arm (Cap 50).

This tailored management should result in a better oncologic prognosis with a lower rate of post therapeutic functional disorders.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed rectal carcinoma

• Primary tumor evaluated by pelvic MR Imaging:

i) iT3 =c tumors, with MRI showing a predictive CRM = 2 mm or a EMS (Extra Mural Spread) = 5 mm

ii) Resectable iT4 tumors (only randomized within the "poor responders" group)

iii) Any T tumors with MRI showing a predictive CRM = 1 mm

• No detectable metastases: Thorax-abdomen-pelvic CT-scan

• Patient = 18 years

• ECOG Performance Status 0-1-2

• Patient information and written informed consent form signed

• Patient who can receive radiotherapy and chemotherapy

• Negative pregnancy test in women of childbearing potential

• Patient covered by a Social Security system

• Hematology : Haemoglobin = 9 g/dL, WBC = 4000/mm3, neutrophils = 1.5 x 109/L, platelets = 100 x 109/L

• Hepatic function : total bilirubin = 1.5 x ULN, AST and ALT = 3 x ULN, Alkaline phosphatases = 3 x ULN

• Renal function : creatinine = 1.25 x ULN or creatinine clearance = 60 ml/min

Exclusion Criteria:

• Indication for immediate surgery

• Primary tumor not measured at the MRI before inclusion

• Previous pelvic radiotherapy

• Contraindication to radiotherapy and/or chemotherapy

• Severe renal or liver impairment

• Cardiac and/or coronary disease which could contraindicate 5-Fu administration

• Active infectious disease

• Peripheral sensitive neuropathy

• History of prior cancer (except if it was cured more than 5 years ago, and if complete remission)

• Patient (male or female) of reproductive potential not using an effective contraceptive method during the whole treatment and up to 6 months after the completion of treatment

• Concurrent participation in any other clinical trial likely to interfere with the therapeutic schedule

• Fertile female patient not using adequate contraception, or breast-feeding woman

Related Conditions & MeSH terms

• Carcinoma
• Locally Advanced Malignant Neoplasm
• Neoplasms
• Rectal Carcinoma
• Rectal Neoplasms

Intervention

Drug:
• Induction trichemotherapy - FOLFIRINOX regimen
A short (4 cycles) and intensive trichemotherapy combinig irinotecan 180 mg/m2, oxaliplatin 85 mg/m2, elvorin 200 mg/m2, 5-Fu (bolus 400 mg/m2, followed by a 46-hour continuous infusion 2,400 mg/m2) will be delivered for 8 weeks (D1=D15).

Other:
• Early tumor response evaluation by MRI volumetry
Two weeks after the CT completion, the tumor volume will be measured by MRI with specific software which automatically borders the tumor so as to determine the early tumor response. A centralized reassessment of all MRI exams will be systematically performed by two radiologists of the coordinator center.

Radiation:
• Radiochemotherapy Cap 50
RCT Cap 50 will combine radiotherapy at a dose of 50 Gy by either conventional 3D or IMRT (2 Gy per fraction, 5 fractions per week during 5 weeks / 44 Gy in mini pelvis, and boost 6 Gy on reduced peritumoral volume) with concomitant oral capecitabine at 1600 mg/m2 per day delivered the days of RT treatment (2 daily intake).
• Radiochemotherapy Cap 60
RCT Cap 60 will combine radiotherapy at a dose of 60 Gy by either conventional 3D or IMRT (2 Gy per fraction, 5 fractions per week during 6 weeks / 44 Gy in mini pelvis, and boost 16 Gy on reduced peritumoral volume) with concomitant oral capecitabine at 1600 mg/m2 per day delivered the days of RT treatment (2 daily intake)

Procedure:
• Radical proctectomy with total mesorectal excision
The proctectomy can be performed by laparoscopic surgery or conventional laparotomy.

Locations

Country	Name	City	State
France	CRLC Val d'Aurelle-Paul Lamarque	Montpellier

Sponsors (1)

Lead Sponsor	Collaborator
Institut du Cancer de Montpellier - Val d'Aurelle

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ro resection rate	To confirm the feasibility of a tailored management with a 90% R0 resection rate achieved for all arms.	Within 15 days after surgery
Secondary	Efficiency of MRI for prognosis	To specify the efficiency of MRI for prognosis in terms of volumetry, downstaging, downsizing and CRM measurement after completion of the induction trichemotherapy.	Within 15 days after the surgery
Secondary	Compliance rate with neoadjuvant treatment schedule	To measure the compliance rate to the whole neoadjuvant schedule (induction CT + radiochemotherapy)	Within 4 months after the start of treatment
Secondary	Acute and late toxicity of neoadjuvant treatments	To evaluate overall toxicity of neoadjuvant treatments (induction trichemotherapy + radiochemotherapy) according to the Common Terminology Criteria for Adverse Events v4.0 (NCI CTC v4.0).	For the duration of treatment, as expexcted to be up to 4 months and within the 5-year follow-up
Secondary	Pathological complete response rate	To assess the pathological complete response rate (ypT0N0)	Within 15 days after surgery
Secondary	Tumor regression grade (TRG)	To assess at pathologic examination the tumor regression grade (TRG) according to the Dworak classification.	Within 15 days after surgery
Secondary	Perioperative and postoperative morbidity	To assess the impact of the therapeutic strategy on perioperative and postoperative morbidity.	Within 6 weeks after surgery and during the 5-year follow-up
Secondary	Sphincter-saving surgery rate	To assess the impact of the therapeutic strategy on the rate of sphincter-saving surgery.	Up to 2 months after the end of the neoadjuvant treatment
Secondary	Functional outcome	To assess the long-term digestive,urinary and sexual functional results of tailored strategy	For a 5-year follow-up
Secondary	Quality of life	To assess the impact of treatments on quality of life according to the EORTC QLQ-C30.	For a 5-year follow-up
Secondary	Local recurrence rate	To measure the local recurrence rate in each treatment arm.	For a 5-year follow-up
Secondary	Incidence of metastases	To measure the incidence of distant metastases (liver, pulmonary, peritoneal, ganglionnary or any others) in each treatment arm.	For a 5-year follow-up