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Locally Advanced Malignant NeoplasmPhase 2GRECCAR4NCT01333709

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

A Phase 2 study testing Induction trichemotherapy - FOLFIRINOX regimen, Early tumor response evaluation by MRI volumetry and Radiochemotherapy Cap 50 in people with Locally Advanced Malignant Neoplasm and Rectal Carcinoma, run by Institut du Cancer de Montpellier - Val d'Aurelle at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Induction trichemotherapy - FOLFIRINOX regimen, Early tumor response evaluation by MRI volumetry and Radiochemotherapy Cap 50
Could I receive a placebo?
No, everyone receives an active treatment
How many people
150 participants
Where
1 siteFrance
Study dates
May 2011to Sep 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed rectal carcinoma
  • Primary tumor evaluated by pelvic MR Imaging:
  • iT3 ≥c tumors, with MRI showing a predictive CRM ≤ 2 mm or a EMS (Extra Mural Spread) ≥ 5 mm
  • Resectable iT4 tumors (only randomized within the "poor responders" group)
  • Any T tumors with MRI showing a predictive CRM ≤ 1 mm
  • No detectable metastases: Thorax-abdomen-pelvic CT-scan
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

France1 site
  • CRLC Val d'Aurelle-Paul Lamarque

    Montpellier, 34298

Other trials in France

About this study

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

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

Read the detailed 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.

Being tested
Induction trichemotherapy - FOLFIRINOX regimen, Early tumor response evaluation by MRI volumetry, Radiochemotherapy Cap 50, Radiochemotherapy Cap 60, Radical proctectomy with total mesorectal excision
Keywords
locally advanced rectal carcinoma, Tailored treatment strategy, MRI volumetry, Early tumor response
Medical subject headings
Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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).

  • 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.

  • 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).

  • 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)

  • Radical proctectomy with total mesorectal excisionProcedure or surgery

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

Study groups in NCT01333709
Study groupRoleWhat they receive
Arm A: immediate rectal surgeryExperimental"Very good" responder patients will be randomly assigned to proctectomy within 2-4 weeks after the end of the induction chemotherapy.
Receives: Drug: Induction trichemotherapy - FOLFIRINOX regimen; Other: Early tumor response evaluation by MRI volumetry; Procedure: Radical proctectomy with total mesorectal excision
Arm B: RCT Cap 50 and then rectal surgeryOther"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).
Receives: Drug: Induction trichemotherapy - FOLFIRINOX regimen; Other: Early tumor response evaluation by MRI volumetry; Radiation: Radiochemotherapy Cap 50; Procedure: Radical proctectomy with total mesorectal excision
Arm C: RCT Cap 50 and then rectal surgeryOther"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).
Receives: Drug: Induction trichemotherapy - FOLFIRINOX regimen; Other: Early tumor response evaluation by MRI volumetry; Radiation: Radiochemotherapy Cap 50; Procedure: Radical proctectomy with total mesorectal excision
Bras D: RCT Cap 60 and then rectal surgeryExperimental"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).
Receives: Drug: Induction trichemotherapy - FOLFIRINOX regimen; Other: Early tumor response evaluation by MRI volumetry; Radiation: Radiochemotherapy Cap 60; Procedure: Radical proctectomy with total mesorectal excision

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ro resection rate

    To confirm the feasibility of a tailored management with a 90% R0 resection rate achieved for all arms.

    Measured: Within 15 days after surgery

Secondary outcomes (11)
  1. 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.

    Measured: Within 15 days after the surgery

  2. Compliance rate with neoadjuvant treatment schedule

    To measure the compliance rate to the whole neoadjuvant schedule (induction CT + radiochemotherapy)

    Measured: Within 4 months after the start of treatment

  3. 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).

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

  4. Pathological complete response rate

    To assess the pathological complete response rate (ypT0N0)

    Measured: Within 15 days after surgery

  5. Tumor regression grade (TRG)

    To assess at pathologic examination the tumor regression grade (TRG) according to the Dworak classification.

    Measured: Within 15 days after surgery

  6. Perioperative and postoperative morbidity

    To assess the impact of the therapeutic strategy on perioperative and postoperative morbidity.

    Measured: Within 6 weeks after surgery and during the 5-year follow-up

  7. Sphincter-saving surgery rate

    To assess the impact of the therapeutic strategy on the rate of sphincter-saving surgery.

    Measured: Up to 2 months after the end of the neoadjuvant treatment

  8. Functional outcome

    To assess the long-term digestive,urinary and sexual functional results of tailored strategy

    Measured: For a 5-year follow-up

  9. Quality of life

    To assess the impact of treatments on quality of life according to the EORTC QLQ-C30.

    Measured: For a 5-year follow-up

  10. Local recurrence rate

    To measure the local recurrence rate in each treatment arm.

    Measured: For a 5-year follow-up

  11. Incidence of metastases

    To measure the incidence of distant metastases (liver, pulmonary, peritoneal, ganglionnary or any others) in each treatment arm.

    Measured: For a 5-year follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Apr 2011 (estimated)
  2. Study startMay 2011
  3. Primary completionSep 2014
  4. Study completionSep 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
150 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01333709
Sponsor's protocol ID
GRECCAR 4
Other IDs
2010-023546-73
Acronym
GRECCAR4
Status last verified
Aug 2017
First submitted
8 Apr 2011
Last updated
21 Aug 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 34759247
  • 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.

    PubMed 28594714

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Induction trichemotherapy - FOLFIRINOX regimen, Early tumor response evaluation by MRI volumetry and Radiochemotherapy Cap 50 in people with Locally Advanced Malignant Neoplasm and Rectal Carcinoma, run by Institut du Cancer de Montpellier - Val d'Aurelle at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ro resection rate (time frame: Within 15 days after surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01333709, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2017.

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