NCT01333709

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
150

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started May 2011

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 8, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

April 12, 2011

Completed
19 days until next milestone

Study Start

First participant enrolled

May 1, 2011

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2014

Completed
Last Updated

August 21, 2017

Status Verified

August 1, 2017

Enrollment Period

3.3 years

First QC Date

April 8, 2011

Last Update Submit

August 16, 2017

Conditions

Locally Advanced Malignant NeoplasmRectal Carcinoma

Keywords

locally advanced rectal carcinomaTailored treatment strategyMRI volumetryEarly tumor response

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (11)

  • Efficiency of MRI for prognosis

    Within 15 days after the surgery

  • Compliance rate with neoadjuvant treatment schedule

    Within 4 months after the start of treatment

  • Acute and late toxicity of neoadjuvant treatments

    For the duration of treatment, as expexcted to be up to 4 months and within the 5-year follow-up

  • Pathological complete response rate

    Within 15 days after surgery

  • Tumor regression grade (TRG)

    Within 15 days after surgery

  • +6 more secondary outcomes

Study Arms (4)

Arm A: immediate rectal surgery

EXPERIMENTAL

"Very good" responder patients will be randomly assigned to proctectomy within 2-4 weeks after the end of the induction chemotherapy.

Drug: Induction trichemotherapy - FOLFIRINOX regimenOther: Early tumor response evaluation by MRI volumetryProcedure: Radical proctectomy with total mesorectal excision

Arm B: RCT Cap 50 and then rectal surgery

OTHER

"Very good" responder patients will be randomly assigned to receive chemoradiotherapy combining the administration of oral capecitabine (1600 mg/m2/day, BID) and radiotherapy at a total dose of 50 grays (2Gy/day, 5 days a week, 5 weeks, boost 6 Gy).

Drug: Induction trichemotherapy - FOLFIRINOX regimenOther: Early tumor response evaluation by MRI volumetryRadiation: Radiochemotherapy Cap 50Procedure: Radical proctectomy with total mesorectal excision

Arm C: RCT Cap 50 and then rectal surgery

OTHER

"Good or poor" responder patients will be randomly assigned to receive chemoradiotherapy combining the administration of oral capecitabine (1600 mg/m2/day, BID) and radiotherapy at a total dose of 50 grays (2Gy/day, 5 days a week, 5 weeks, boost 6 Gy).

Drug: Induction trichemotherapy - FOLFIRINOX regimenOther: Early tumor response evaluation by MRI volumetryRadiation: Radiochemotherapy Cap 50Procedure: Radical proctectomy with total mesorectal excision

Bras D: RCT Cap 60 and then rectal surgery

EXPERIMENTAL

"Good or poor" responder patients will be randomly assigned to receive chemoradiotherapy combining the administration of oral capecitabine (1600 mg/m2/day, BID) and radiotherapy at a total dose of 60 grays (2Gy/day, 5 days a week, 6 weeks, boost 14 Gy).

Drug: Induction trichemotherapy - FOLFIRINOX regimenOther: Early tumor response evaluation by MRI volumetryRadiation: Radiochemotherapy Cap 60Procedure: Radical proctectomy with total mesorectal excision

Interventions

Induction trichemotherapy - FOLFIRINOX regimenDRUG

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).

Arm A: immediate rectal surgeryArm B: RCT Cap 50 and then rectal surgeryArm C: RCT Cap 50 and then rectal surgeryBras D: RCT Cap 60 and then rectal surgery
Early tumor response evaluation by MRI volumetryOTHER

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.

Arm A: immediate rectal surgeryArm B: RCT Cap 50 and then rectal surgeryArm C: RCT Cap 50 and then rectal surgeryBras D: RCT Cap 60 and then rectal surgery
Radiochemotherapy Cap 50RADIATION

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).

Arm B: RCT Cap 50 and then rectal surgeryArm C: RCT Cap 50 and then rectal surgery
Radiochemotherapy Cap 60RADIATION

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)

Bras D: RCT Cap 60 and then rectal surgery
Radical proctectomy with total mesorectal excisionPROCEDURE

The proctectomy can be performed by laparoscopic surgery or conventional laparotomy.

Arm A: immediate rectal surgeryArm B: RCT Cap 50 and then rectal surgeryArm C: RCT Cap 50 and then rectal surgeryBras D: RCT Cap 60 and then rectal surgery

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • Indication for immediate surgery
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

CRLC Val d'Aurelle-Paul Lamarque

Montpellier, 34298, France

Location

Related Publications (2)

  • Rouanet P, Rullier E, Lelong B, Maingon P, Tuech JJ, Pezet D, Castan F, Nougaret S; GRECCAR Study Group*. Tailored Strategy for Locally Advanced Rectal Carcinoma (GRECCAR 4): Long-term Results From a Multicenter, Randomized, Open-Label, Phase II Trial. Dis Colon Rectum. 2022 Aug 1;65(8):986-995. doi: 10.1097/DCR.0000000000002153. Epub 2022 Jul 5.

    PMID: 34759247DERIVED

  • Rouanet P, Rullier E, Lelong B, Maingon P, Tuech JJ, Pezet D, Castan F, Nougaret S; and the GRECCAR Study Group. Tailored Treatment Strategy for Locally Advanced Rectal Carcinoma Based on the Tumor Response to Induction Chemotherapy: Preliminary Results of the French Phase II Multicenter GRECCAR4 Trial. Dis Colon Rectum. 2017 Jul;60(7):653-663. doi: 10.1097/DCR.0000000000000849.

    PMID: 28594714DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesIntestinal DiseasesRectal Diseases

Study Officials

  • Philippe ROUANET, MD, Ph D

    CRLC Val d'Aurelle-Paul Lamarque

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 8, 2011

First Posted

April 12, 2011

Study Start

May 1, 2011

Primary Completion

September 1, 2014

Study Completion

September 1, 2014

Last Updated

August 21, 2017

Record last verified: 2017-08

Locations

FR(1)