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Study Evaluating the Tailored Management of Locally-advanced Rectal Carcinoma

ConditionsLocally Advanced Malignant NeoplasmRectal Carcinoma
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorInstitut du Cancer de Montpellier - Val d'Aurelle

About this trial

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 chemotherapy. 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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Written consent,

Patient who receive Folfirinox,

Patient aged over 18 years old,

World Health Organization (WHO) performance status ≥ 1,

Disqualifiers

None

Trial design

Design model

Parallel

Treatments tested in this trial

  • Induction chemotherapy - modified FOLFIRINOX regimen

    Drug

    An induction chemotherapy (6 cycles) combining irinotecan 180 mg/m2, oxaliplatin 85 mg/m2, elvorin 200 mg/m2 followed by a 46-hour continuous infusion 2,400 mg/m2) will be delivered every 15 days (D1=D15).

  • Early tumor response evaluation by MRI volumetry

    Other intervention

    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

    Radiation

    RCT Cap 50 will combine radiotherapy at a dose of 50 Gy by either conventional 3D or Intensity-Modulated RadioTherapy (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 radiotherapy treatment (2 daily intake).

  • Radical proctectomy with total mesorectal excision

    Procedure/Surgery

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

Treatment groups

1,075 Participants
are divided into 2 treatment groups
Group A: Experimental: Arm A: immediate rectal surgeryExperimental treatment 3 interventions
Group B: RCT Cap 50 and then rectal surgeryActive comparator 4 interventions

Trial outcomes

Primary outcomes

1

R0 resection rate (R0 is defined as Circumferential resection margin (CRM ≥ 1 mm) for Phase II

The excision limits will be determined precisely on the part, after exhaustive sampling of the maximum tumor extension zones and containing the surface of the inked mesorectum.

Time frame
Within 15 days after surgery
2

3-year Disease free survival (DFS) for Phase III

(DFS is defined as the time interval between randomization and the occurrence of the first event, such as local or metastatic recurrence, the development of a second cancer or death from any cause).Locoregional failure include locally progressive disease leading to an unresectable tumour, local R2 resection, or local recurrence after an R0-R1 resection. Patients without events at the time of analysis will be censored on the date of the last informative follow-up.

Time frame
3 years

Secondary outcomes

1

Compliance rate with neoadjuvant treatment schedule

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

Time frame
Within 4.5 months after the start of treatment
2

Pathological complete response rate

To assess the pathological complete response rate (ypT0N0)

Time frame
Within 15 days after surgery
3

Sphincter-saving surgery rate

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

Time frame
Up to 2 months after the end of the neoadjuvant treatment
4

Quality of life by using the quality of life questionnaire score (QLQ-C30)

The EORTC QLQ-C30 uses for the questions 1 to 28 a 4-point scale. The scale scores from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much"). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome. The EORTC QLQ-C30 uses for the questions 29 and 30 a 7-points scale. The scale scores from 1 to 7: 1 ("very poor") to 7 ("excellent"). Half points are not allowed. The range is 6. First of all, raw score has to be calculated with mean values. Afterwards linear transformation is performed to be comparable. More points are considered to have a better outcome.

Time frame
For a 1-year follow-up

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Institut du Cancer de Montpellier - Val d'Aurelle

Lead sponsor

Source ClinicalTrials.gov
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