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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-05-31

Study Completion Date

2014-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Testing Nivolumab and Ipilimumab With Short-Course Radiation in Locally Advanced Rectal Cancer

NCT04751370

Locally Advanced Rectal Adenocarcinoma Stage II Rectal Cancer AJCC v8 Stage III Rectal Cancer AJCC v8

ACTIVE_NOT_RECRUITING PHASE2

Safety and Efficacy of Atezolizumab Combined to Preoperative Radio-chemotherapy in Localized Rectal Cancer

NCT03127007

Rectal Neoplasms

COMPLETED PHASE1/PHASE2

Phase II Study of Irinotecan,Oxaliplatin Plus TS-1 in Untreated Metastatic Colorectal Cancer

NCT00506571

Colorecal Neoplasms Secondary

UNKNOWN PHASE2

Induction Chemotherapy for Locally Recurrent Rectal Cancer

NCT04389086

Recurrent Rectal Cancer

RECRUITING PHASE3

Preoperative Radiotherapy And ASTX660 in Rectum Cancer

NCT05912075

Locally-advanced Rectal Cancer

RECRUITING PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Locally Advanced Malignant Neoplasm Rectal Carcinoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Arm A: immediate rectal surgery

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

Group Type EXPERIMENTAL

Induction trichemotherapy - FOLFIRINOX regimen

Intervention Type DRUG

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 volumetry

Intervention Type OTHER

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.

Radical proctectomy with total mesorectal excision

Intervention Type PROCEDURE

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

Arm B: RCT Cap 50 and then rectal surgery

"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).

Group Type OTHER

Induction trichemotherapy - FOLFIRINOX regimen

Intervention Type DRUG

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 volumetry

Intervention Type OTHER

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 50

Intervention Type RADIATION

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).

Radical proctectomy with total mesorectal excision

Intervention Type PROCEDURE

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

Arm C: RCT Cap 50 and then rectal surgery

"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).

Group Type OTHER

Induction trichemotherapy - FOLFIRINOX regimen

Intervention Type DRUG

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 volumetry

Intervention Type OTHER

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 50

Intervention Type RADIATION

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).

Radical proctectomy with total mesorectal excision

Intervention Type PROCEDURE

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

Bras D: RCT Cap 60 and then rectal surgery

"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).

Group Type EXPERIMENTAL

Induction trichemotherapy - FOLFIRINOX regimen

Intervention Type DRUG

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 volumetry

Intervention Type OTHER

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 60

Intervention Type RADIATION

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 excision

Intervention Type PROCEDURE

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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).

Intervention Type DRUG

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.

Intervention Type OTHER

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).

Intervention Type RADIATION

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)

Intervention Type RADIATION

Radical proctectomy with total mesorectal excision

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

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No