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Study Evaluating the Tailored Management of Locally-advanced Rectal Carcinoma (GRECCAR14)

Primary Purpose

Locally Advanced Malignant Neoplasm, Rectal Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Induction chemotherapy - modified FOLFIRINOX regimen
Early tumor response evaluation by MRI volumetry
Radiochemotherapy Cap 50
Radical proctectomy with total mesorectal excision
Sponsored by
Institut du Cancer de Montpellier - Val d'Aurelle
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Locally Advanced Malignant Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA FOR SCREENING

  1. Screening written consent,
  2. Patient who receive Folfirinox,
  3. Patient aged over 18 years old,
  4. World Health Organization (WHO) performance status ≥ 1,
  5. Histologically confirmed diagnosis of adenocarcinoma of the rectum,
  6. Distal part of the tumor from 1 to 12 cm from the upper part of the levator ani (dynamic rectal examination),
  7. No unequivocal evidence on CT-Scan of established metastatic disease,
  8. MRI evaluation of the locally advanced tumor before neoadjuvant chemotherapy:

    1. Predictive CRM < 2 mm
    2. Or T3c-d (extending ≥ 5 mm beyond the muscularis propria) with extra mural venous invasion (EMVI)
    3. Or T4a-b (except bone and sphincteric invasion),
  9. Active cardiac disease including any of the following: a. Congestive heart failure ≥ New York Heart Association (NYHA) class 2 (appendix 4), b. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), c. Myocardial infarction less than 6 months before first dose of treatment, d. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted),

NON INCLUSION CRITERIA FOR SCREENING

  1. Non measurable rectal tumor or not assessed by MRI before inclusion,
  2. Ultra-low rectal tumor at diagnosis which imposes radiotherapy administration (inferior tumor pole less than 1 cm from the upper part of the levator ani).

INCLUSION CRITERIA FOR EXPERIMENTAL TREATMENT

  1. Written consent for experimental treatment,
  2. WHO performance status 0-1,
  3. Patient with tumoral regression ≥ 60% and CRM ≥ 1mm,
  4. No unequivocal evidence on CT-Scan of established metastatic disease,
  5. General condition considered suitable for radical pelvic surgery and a systemic therapy with Capecitabine
  6. Adequate hematologic, hepatic, renal and ionogram function assessed within 7 days prior to study treatment a. Platelet count ≥ 100,000/mm3; Hemoglobin (Hb) ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥ 1,500/ mm3 b. Total bilirubin ≤ 1.5 x Upper Limit Normal (ULN), Alkaline phosphatases ≤ 3 x ULN and ASpartate aminoTransferase (AST) and ALanine aminoTransferase (ALT) ≤ 3 x ULN, c. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min according to Modification of Diet in Renal Disease (MDRD),
  7. For women of reproductive potential, negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test obtained within 7 days before the start of study treatment. Women not of reproductive potential are female patients who are postmenopausal or permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy),
  8. For women of childbearing potential and men, agreement to use an adequate contraception for the duration of study participation and up to 6 months following completion of therapy. Females of childbearing potential who are sexually active with a non-sterilized male partner must use 2 methods, of effective contraception. The investigator or a designated associate is requested to advise the patient on how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care,
  9. No evidence of chronic or acute ischemic heart disease,
  10. Willing to participate to the study, and able to give informed consent and to comply with the treatment and follow-up schedules,
  11. Affiliation to the French Social Security System.

NON-INCLUSION CRITERIA FOR EXPERIMENTAL TREATMENT

  1. Patient with a history of pelvic radiotherapy,
  2. Contraindication to chemotherapy and/or radiotherapy,
  3. Complete or partial Dihydropyrimidine deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL),
  4. Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to study inclusion, except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non invasive tumor), Tis (carcinoma in situ) and T1 (lamina propria invasion)],
  5. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before start of treatment,
  6. Any infection that could jeopardize treatment administration,
  7. Any other serious concomitant disease or disorder that may interfere with the patient's participation in the study and safety during the study (e.g., severe liver, heart, kidney, lung, metabolic, or psychiatric disorders),
  8. History of inflammatory bowel disease,
  9. Patients with a history of pulmonary fibrosis or interstitial pneumonia,
  10. Patients using antivitamin K (Coumadin etc…) but it's possible to substitute the antivitamin K treatment with low molecular weight heparins (LMWHs) before starting chemotherapy,
  11. Known hypersensitivity to Capecitabine drug, study drug classes, or any constituent of the products,
  12. Patient who received live attenuated vaccine within 10 days of inclusion,
  13. Pregnant or breastfeeding woman. If a patient is of childbearing age, she must have a negative pregnancy test (serum β-hCG) documented 72 hours prior to inclusion,
  14. Patient treated with an investigational drug within the last 30 days,
  15. Patient under curatorship or guardianship or safeguard justice,
  16. Inability to submit to medical monitoring of the trial for geographical, social or psychological reasons.

Sites / Locations

  • Hôpital Nord de Marseille
  • CHU BesançonRecruiting
  • CHU de BordeauxRecruiting
  • Insitut Régional du Cancer de MontpellierRecruiting
  • CHU de NancyRecruiting
  • Centre Alexis VautrinRecruiting
  • Centre Oscart LambretRecruiting
  • CHU AmiensRecruiting
  • CHU Clermont-FerrandRecruiting
  • CHU de LyonRecruiting
  • Ch Annecy
  • CHU RouenRecruiting
  • Hôpital BicêtreRecruiting
  • Bordeaux Colorectal InstituteRecruiting
  • Centre Georges-François Leclerc
  • Chu GrenobleRecruiting
  • Chu LilleRecruiting
  • CAC Léon BérardRecruiting
  • Hôpital La TimoneRecruiting
  • Centre Antoine LacassagneRecruiting
  • CHU de NîmesRecruiting
  • Hôpital Saint-LouisRecruiting
  • Hôpital Saint-AntoineRecruiting
  • Hôpital Européen Georges-PompidouRecruiting
  • Hôpital DiaconessesRecruiting
  • Institut de Cancérologie de l'OuestRecruiting
  • CHU de ToulouseRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Experimental: Arm A: immediate rectal surgery

RCT Cap 50 and then rectal surgery

Arm Description

"Very good" responder patients will be randomly assigned to proctectomy performed within 4 to 6 weeks from randomization.

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) followed after 7 weeks by a proctectomy.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Compliance rate with neoadjuvant treatment schedule
To measure the compliance rate to the whole neoadjuvant schedule (induction CT + radiochemotherapy)
Pathological complete response rate
To assess the pathological complete response rate (ypT0N0)
Sphincter-saving surgery rate
To assess the impact of the therapeutic strategy on the rate of sphincter-saving surgery.
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.
Bowel function, Low anterior resection syndrome (LARS)
Assessed using LARS questionnaire (score 0-42, a high score indicates poor bowel function)
Quality of life by using the quality of life questionnaire score (QLQ-CR29)
Score 26-108, a high score indicates many symptoms of colorectal cancer.
3-year local recurrence free survival rate (L-RFS)
The time interval from the date of randomization to the date of local recurrence or death from any cause).Patients alive without local recurrence will be censored at the date of last follow-up.
3-year metastasis recurrence free survival rate (M-RFS)
The time interval from the date of randomization to the date of metastatic recurrence or death from any cause).Patients alive without metastasis will be censored at the date of last follow-up.
3-year Overall survival (OS)
The time interval from the date of randomization to the date of death from any cause. Patients alive will be censored at the date of last follow-up.
5-year Overall survival (OS)
The time interval from the date of randomization to the date of death from any cause. Patients alive will be censored at the date of last follow-up.
Local recurrence rate
The time interval from the date of randomization to the date of local recurrence. Patients without local recurrence will be censored at the date of last follow-up or death.
Clavien-Dindo grade
Grade 1 (light) to Grade 5 = Death of patient . It is widely used throughout surgery for grading adverse events (i.e. complications) which occur as a result of surgical procedures.
Neoadjuvant rectal Score by Fokas
The score uses the variables of clinical tumor stage, pathologic tumor stage, and pathologic nodal stage which are commonly available, furthering its utility in the clinical setting. The final scores range from 0 (good prognostic) to 100 (poor prognostic).
Rates of Total mesorectal excision (TME) grading according to Quirke
This grade is given by the pathologist on the appearance of the mesorectum on fresh specimen (complete grade = good resection), incomplete and near incomplete grade (between good and poor resection), incomplete grade = poor resection)
Distal margin to the tumor
Definitive stoma rate
Second surgery rate
Rehospitalization rate
Dworak Classification
Histopathologic analysis of tumor. Grade 0 to grade 4 with (Grade 4 = sterilized tumor to grade 0 = no regression of tumor)
Metastasis recurrence rate
the time to metastasis defined as the time interval from the date of randomization to the date of metastasis. Patients without metastasis will be censored at the date of last follow-up or death.
Disease Fee Survival rate (DFS)
the time interval from the date of randomization until the date of the first cancer-related event, or death from any cause). Patients alive without event will be censored at the date of last follow-up.
Assessment of adverse events by using the NCI-CTCAE version 5 scale
From the signature of informed consent until 60 days after Surgery
Evaluation of urinary function by International Prostate Symptom Score (IPSS) questionnaire score
Score 0-35, a high score indicates an impaired urinary function.
Evaluation of sexual function in men by International Index of Erectile Function (IIEFS) questionnaire score
Score 1-25, a low score indicates an impaired sexual function in men.
Evaluation of sexual function in women by Female Sexual Function Index (FSFI) questionnaire score
Score 4-95, a low score indicates an impaired sexual function in women.

Full Information

First Posted
February 5, 2021
Last Updated
September 26, 2023
Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle
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1. Study Identification

Unique Protocol Identification Number
NCT04749108
Brief Title
Study Evaluating the Tailored Management of Locally-advanced Rectal Carcinoma
Acronym
GRECCAR14
Official Title
Multicentric Phase II-III Study Evaluating the Tailored Management of Locally-advanced Rectal Carcinoma After a Favorable Response to Induction Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 26, 2021 (Actual)
Primary Completion Date
August 2027 (Anticipated)
Study Completion Date
August 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).
Detailed Description
Cancer of the rectum is a common disease. It affects nearly 15,000 new people each year, with more men (53%) than women (47%). In more than 9 out of 10 cases, it occurs after 50 years. Three types of treatments are used to treat rectal cancer: surgery, radiotherapy and drug treatments. The standard treatment for Locally Advanced Rectal Cancers (LARC) is multidisciplinary, combining chemotherapy, radiotherapy and surgery. The usual treatment in this situation is called induction chemotherapy administrated before radiochemotherapy. This phase of treatment taking place before surgery is called neoadjuvant therapy. However, treating all cancers of the locally advanced rectum with the same neoadjuvant treatment exposes patients who are good responders to neoadjuvant chemotherapy with possible toxicity to radiotherapy and patients who are poor responders to ineffectiveness of conventional radiotherapy with surgery and so to a mutilating ineffective treatment. The short- and long-term toxicity of pelvic radiation may be the most compelling reason to reconsider reflexive neoadjuvant radiochemotherapy (NA-RCT) and to move toward a more individualized approach. A large North American trial is currently evaluating the suppression of preoperative radiation therapy in patients selected as a good responder to induction chemotherapy. A first trial called GRECCAR-4 (Surgical Research Group on Rectum CAncer) with induction chemotherapy by 5 Fluorouracil + Irinotecan + Oxaliplatin and personalized radiochemotherapy reported the following results: High-dose induction chemotherapy is well tolerated and reproducible Early assessment after neo-adjuvant chemotherapy makes it possible to discriminate between good and bad responders without a negative impact on surgery. Personalized management of LARC according to the early tumor response to chemotherapy is possible. In good responder patients, a resection rate of 100% was achieved (even in the arm without radiotherapy), but due to poor recruitment, it is not possible to draw a formal conclusion regarding these promising results. The oncological results at 5 years show a local recurrence rate of 0% for the good responders and 4.8% for the poor responders. The 5-year overall survival was 86.7% with a 5-year progression-free survival of 75.0%. GRECCAR 14 is the only French trial to question the feasibility of appropriate management of non-metastatic LARC. Its main objective is to evaluate, in good responder patients, personalized management after preoperative CT treatment. GRECCAR-14 will try to confirm this strategy taking into account the 1st results of GRECCAR 4. The study will initially focus on 200 patients to assess the surgical quality of this therapeutic strategy and then on 230 additional patients to assess the effectiveness of this personalized treatment on survival without recurrence.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Malignant Neoplasm, Rectal Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Drug: Induction chemotherapy - modified FOLFIRINOX regimen Other: Early tumor response evaluation by MRI volumetry Radiation: Radiochemotherapy Cap 50 Procedure: Radical proctectomy with total mesorectal excision
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1075 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental: Arm A: immediate rectal surgery
Arm Type
Experimental
Arm Description
"Very good" responder patients will be randomly assigned to proctectomy performed within 4 to 6 weeks from randomization.
Arm Title
RCT Cap 50 and then rectal surgery
Arm Type
Active Comparator
Arm Description
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) followed after 7 weeks by a proctectomy.
Intervention Type
Drug
Intervention Name(s)
Induction chemotherapy - modified FOLFIRINOX regimen
Intervention Description
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).
Intervention Type
Other
Intervention Name(s)
Early tumor response evaluation by MRI volumetry
Intervention Description
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
Radiation
Intervention Name(s)
Radiochemotherapy Cap 50
Intervention Description
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).
Intervention Type
Procedure
Intervention Name(s)
Radical proctectomy with total mesorectal excision
Intervention Description
The proctectomy can be performed by laparoscopic surgery or conventional laparotomy.
Primary Outcome Measure Information:
Title
R0 resection rate (R0 is defined as Circumferential resection margin (CRM ≥ 1 mm) for Phase II
Description
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
Title
3-year Disease free survival (DFS) for Phase III
Description
(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 Outcome Measure Information:
Title
Compliance rate with neoadjuvant treatment schedule
Description
To measure the compliance rate to the whole neoadjuvant schedule (induction CT + radiochemotherapy)
Time Frame
Within 4.5 months after the start of treatment
Title
Pathological complete response rate
Description
To assess the pathological complete response rate (ypT0N0)
Time Frame
Within 15 days after surgery
Title
Sphincter-saving surgery rate
Description
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
Title
Quality of life by using the quality of life questionnaire score (QLQ-C30)
Description
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
Title
Bowel function, Low anterior resection syndrome (LARS)
Description
Assessed using LARS questionnaire (score 0-42, a high score indicates poor bowel function)
Time Frame
For a 1-year follow-up
Title
Quality of life by using the quality of life questionnaire score (QLQ-CR29)
Description
Score 26-108, a high score indicates many symptoms of colorectal cancer.
Time Frame
For a 1-year follow-up
Title
3-year local recurrence free survival rate (L-RFS)
Description
The time interval from the date of randomization to the date of local recurrence or death from any cause).Patients alive without local recurrence will be censored at the date of last follow-up.
Time Frame
3 years
Title
3-year metastasis recurrence free survival rate (M-RFS)
Description
The time interval from the date of randomization to the date of metastatic recurrence or death from any cause).Patients alive without metastasis will be censored at the date of last follow-up.
Time Frame
3 years
Title
3-year Overall survival (OS)
Description
The time interval from the date of randomization to the date of death from any cause. Patients alive will be censored at the date of last follow-up.
Time Frame
3 years
Title
5-year Overall survival (OS)
Description
The time interval from the date of randomization to the date of death from any cause. Patients alive will be censored at the date of last follow-up.
Time Frame
5 years
Title
Local recurrence rate
Description
The time interval from the date of randomization to the date of local recurrence. Patients without local recurrence will be censored at the date of last follow-up or death.
Time Frame
For a 2-3-year follow-up
Title
Clavien-Dindo grade
Description
Grade 1 (light) to Grade 5 = Death of patient . It is widely used throughout surgery for grading adverse events (i.e. complications) which occur as a result of surgical procedures.
Time Frame
Within 1 month after surgery
Title
Neoadjuvant rectal Score by Fokas
Description
The score uses the variables of clinical tumor stage, pathologic tumor stage, and pathologic nodal stage which are commonly available, furthering its utility in the clinical setting. The final scores range from 0 (good prognostic) to 100 (poor prognostic).
Time Frame
Within 15 days after surgery
Title
Rates of Total mesorectal excision (TME) grading according to Quirke
Description
This grade is given by the pathologist on the appearance of the mesorectum on fresh specimen (complete grade = good resection), incomplete and near incomplete grade (between good and poor resection), incomplete grade = poor resection)
Time Frame
Within 15 days after surgery
Title
Distal margin to the tumor
Time Frame
Within 15 days after surgery
Title
Definitive stoma rate
Time Frame
36 MONTHS
Title
Second surgery rate
Time Frame
36 MONTHS
Title
Rehospitalization rate
Time Frame
Within 1 month after surgery
Title
Dworak Classification
Description
Histopathologic analysis of tumor. Grade 0 to grade 4 with (Grade 4 = sterilized tumor to grade 0 = no regression of tumor)
Time Frame
Approximately 6 weeks after randomization
Title
Metastasis recurrence rate
Description
the time to metastasis defined as the time interval from the date of randomization to the date of metastasis. Patients without metastasis will be censored at the date of last follow-up or death.
Time Frame
For a 2-3-year follow-up
Title
Disease Fee Survival rate (DFS)
Description
the time interval from the date of randomization until the date of the first cancer-related event, or death from any cause). Patients alive without event will be censored at the date of last follow-up.
Time Frame
For a 3-year follow-up
Title
Assessment of adverse events by using the NCI-CTCAE version 5 scale
Description
From the signature of informed consent until 60 days after Surgery
Time Frame
Approximately 72 months for all patients
Title
Evaluation of urinary function by International Prostate Symptom Score (IPSS) questionnaire score
Description
Score 0-35, a high score indicates an impaired urinary function.
Time Frame
For a 1-year follow-up
Title
Evaluation of sexual function in men by International Index of Erectile Function (IIEFS) questionnaire score
Description
Score 1-25, a low score indicates an impaired sexual function in men.
Time Frame
For a 1-year follow-up
Title
Evaluation of sexual function in women by Female Sexual Function Index (FSFI) questionnaire score
Description
Score 4-95, a low score indicates an impaired sexual function in women.
Time Frame
For a 1-year follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA FOR SCREENING Written consent, Patient who receive Folfirinox, Patient aged over 18 years old, World Health Organization (WHO) performance status ≥ 1, Histologically confirmed diagnosis of adenocarcinoma of the rectum, Distal part of the tumor from 1 to 12 cm from the upper part of the levator ani (dynamic rectal examination), No unequivocal evidence on CT-Scan of established metastatic disease, MRI evaluation of the locally advanced tumor before neoadjuvant chemotherapy: Predictive CRM < 2 mm Or T3c-d (extending ≥ 5 mm beyond the muscularis propria) with extra mural venous invasion (EMVI) Or T4a-b (except bone and sphincteric invasion). NON INCLUSION CRITERIA FOR SCREENING Non measurable rectal tumor or not assessed by MRI before inclusion, Ultra-low rectal tumor at diagnosis which imposes radiotherapy administration (inferior tumor pole less than 1 cm from the upper part of the levator ani). Active cardiac disease including any of the following: a. Congestive heart failure ≥ New York Heart Association (NYHA) class 2 (appendix 4), b. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), c. Myocardial infarction less than 6 months before first dose of treatment, d. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted), Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to study inclusion, except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non invasive tumor), Tis (carcinoma in situ) and T1 (lamina propria invasion)], Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before start of treatment. INCLUSION CRITERIA FOR EXPERIMENTAL TREATMENT WHO performance status 0-1, Patient with tumoral regression ≥ 60% and CRM ≥ 1mm, No unequivocal evidence on CT-Scan of established metastatic disease, General condition considered suitable for radical pelvic surgery and a systemic therapy with Capecitabine Adequate hematologic, hepatic, renal and ionogram function assessed within 7 days prior to study treatment a. Platelet count ≥ 100,000/mm3; Hemoglobin (Hb) ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥ 1,500/ mm3 b. Total bilirubin ≤ 1.5 x Upper Limit Normal (ULN), Alkaline phosphatases ≤ 3 x ULN and ASpartate aminoTransferase (AST) and ALanine aminoTransferase (ALT) ≤ 3 x ULN, c. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min according to Modification of Diet in Renal Disease (MDRD), For women of reproductive potential, negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test obtained within 7 days before the start of study treatment. Women not of reproductive potential are female patients who are postmenopausal or permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy), For women of childbearing potential and men, agreement to use an adequate contraception for the duration of study participation and up to 6 months following completion of therapy. Females of childbearing potential who are sexually active with a non-sterilized male partner must use 2 methods, of effective contraception. The investigator or a designated associate is requested to advise the patient on how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care, No evidence of chronic or acute ischemic heart disease, Willing to participate to the study, and able to give informed consent and to comply with the treatment and follow-up schedules, Affiliation to the French Social Security System. NON-INCLUSION CRITERIA FOR EXPERIMENTAL TREATMENT Patient with a history of pelvic radiotherapy, Contraindication to chemotherapy and/or radiotherapy, Complete or partial Dihydropyrimidine deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL), Any infection that could jeopardize treatment administration, Any other serious concomitant disease or disorder that may interfere with the patient's participation in the study and safety during the study (e.g., severe liver, heart, kidney, lung, metabolic, or psychiatric disorders), History of inflammatory bowel disease, Patients with a history of pulmonary fibrosis or interstitial pneumonia, Patients using antivitamin K (Coumadin etc…) but it's possible to substitute the antivitamin K treatment with low molecular weight heparins (LMWHs) before starting chemotherapy, Known hypersensitivity to Capecitabine drug, study drug classes, or any constituent of the products, Patient who received live attenuated vaccine within 10 days of inclusion, Pregnant or breastfeeding woman. If a patient is of childbearing age, she must have a negative pregnancy test (serum β-hCG) documented 72 hours prior to inclusion, Patient treated with an investigational drug within the last 30 days, Patient under curatorship or guardianship or safeguard justice, Inability to submit to medical monitoring of the trial for geographical, social or psychological reasons.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Philippe Rouanet, MD
Phone
4 67 61 30 71
Ext
+33
Email
Philippe.Rouanet@icm.unicancer.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philippe Rouanet, MD
Organizational Affiliation
Philippe.Rouanet@icm.unicancer.fr
Official's Role
Study Chair
Facility Information:
Facility Name
Hôpital Nord de Marseille
City
Marseille
State/Province
Bouches Du Rhône
ZIP/Postal Code
13015
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laura Beyer-Berjot, MD
Facility Name
CHU Besançon
City
Besançon
State/Province
Doubs
ZIP/Postal Code
25030
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zaher Lakkis, MD
Facility Name
CHU de Bordeaux
City
Bordeaux
State/Province
Gironde
ZIP/Postal Code
33600
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bernard Celerier, MS
Facility Name
Insitut Régional du Cancer de Montpellier
City
Montpellier
State/Province
Hérault
ZIP/Postal Code
34298
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe Rouanet, MD
Phone
04-67-61-31-50
Ext
+33
Email
Philippe.Rouanet@icm.unicancer.fr
First Name & Middle Initial & Last Name & Degree
Philippe Rouanet, MD
Facility Name
CHU de Nancy
City
Vandœuvre-lès-Nancy
State/Province
Lorraine
ZIP/Postal Code
54511
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adeline Germain, MD
Facility Name
Centre Alexis Vautrin
City
Nancy
State/Province
Meurthe Et Moselle
ZIP/Postal Code
54519
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frédéric Marchal, MD
Facility Name
Centre Oscart Lambret
City
Lille
State/Province
Nord
ZIP/Postal Code
59000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mehrdad Jafari, MD
Facility Name
CHU Amiens
City
Amiens
State/Province
Picardie
ZIP/Postal Code
80054
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Marc Regimbeau, MD
Facility Name
CHU Clermont-Ferrand
City
Clermont-Ferrand
State/Province
Puy De Dôme
ZIP/Postal Code
63000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne Dubois, MD
Facility Name
CHU de Lyon
City
Lyon
State/Province
Rhône
ZIP/Postal Code
69310
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eddy Cotte, MD
Facility Name
Ch Annecy
City
Annecy
State/Province
Savoie
ZIP/Postal Code
74330
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mathieu Baconnier, MD
Facility Name
CHU Rouen
City
Rouen
State/Province
Seine-Maritime
ZIP/Postal Code
76031
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Jacques Tuech, MD
Facility Name
Hôpital Bicêtre
City
Le Kremlin-Bicêtre
State/Province
Val De Marne
ZIP/Postal Code
94270
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antoine Brouquet, MD
Facility Name
Bordeaux Colorectal Institute
City
Bordeaux
ZIP/Postal Code
33300
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Quentin Denost, MD
Facility Name
Centre Georges-François Leclerc
City
Dijon
ZIP/Postal Code
21079
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cédric Chevalier, MD
Facility Name
Chu Grenoble
City
Grenoble
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bertrand Trilling, MD
Facility Name
Chu Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guillaume Piessen, MD
Facility Name
CAC Léon Bérard
City
Lyon
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michel Rivoire, MD
First Name & Middle Initial & Last Name & Degree
Michel Rivoire, MD
Facility Name
Hôpital La Timone
City
Marseille
ZIP/Postal Code
13005
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laetitia Dahan, MD
Facility Name
Centre Antoine Lacassagne
City
Nice
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ludovic Evesque, MD
Facility Name
CHU de Nîmes
City
Nîmes
ZIP/Postal Code
30029
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Bertrand, MD
Facility Name
Hôpital Saint-Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Léon Maggiori, MD
Facility Name
Hôpital Saint-Antoine
City
Paris
ZIP/Postal Code
75012
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jérémie Lefèvre, MD
Facility Name
Hôpital Européen Georges-Pompidou
City
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mehdi Karoui, MD
Facility Name
Hôpital Diaconesses
City
Paris
ZIP/Postal Code
75020
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alain Valverde, MD
Facility Name
Institut de Cancérologie de l'Ouest
City
Saint-Herblain
ZIP/Postal Code
44800
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frédéric Dumont, MD
Facility Name
CHU de Toulouse
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laurent Ghouti, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All data will be available after publication of the results in peer-reviewed revues, and in national and international meetings. It includes all disidentified participants' data, the study protocol, the statistical analysis plan and the analytic code. The corresponding author will provide data and datasets generated and/or analyzed during the study upon reasonable request.
IPD Sharing Time Frame
Access to study data upon written detailed request sent to ICM, following publication and until 5 years after publication of summary data.
IPD Sharing Access Criteria
The data shared will be limited to that required for independent mandated verification of the published results, the applicant will need authorization from ICM for personal access, and data will only be transferred after signing of a data access agreement.
Citations:
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Rodel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Strobel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. doi: 10.1016/S1470-2045(15)00159-X. Epub 2015 Jul 15.
Results Reference
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PubMed Identifier
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Citation
Martin ST, Heneghan HM, Winter DC. Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. Br J Surg. 2012 Jul;99(7):918-28. doi: 10.1002/bjs.8702. Epub 2012 Feb 23.
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PubMed Identifier
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Citation
Bregendahl S, Emmertsen KJ, Lous J, Laurberg S. Bowel dysfunction after low anterior resection with and without neoadjuvant therapy for rectal cancer: a population-based cross-sectional study. Colorectal Dis. 2013 Sep;15(9):1130-9. doi: 10.1111/codi.12244.
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Citation
Chen TY, Wiltink LM, Nout RA, Meershoek-Klein Kranenbarg E, Laurberg S, Marijnen CA, van de Velde CJ. Bowel function 14 years after preoperative short-course radiotherapy and total mesorectal excision for rectal cancer: report of a multicenter randomized trial. Clin Colorectal Cancer. 2015 Jun;14(2):106-14. doi: 10.1016/j.clcc.2014.12.007. Epub 2014 Dec 31.
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PubMed Identifier
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Citation
Schrag D, Weiser MR, Goodman KA, Gonen M, Hollywood E, Cercek A, Reidy-Lagunes DL, Gollub MJ, Shia J, Guillem JG, Temple LK, Paty PB, Saltz LB. Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol. 2014 Feb 20;32(6):513-8. doi: 10.1200/JCO.2013.51.7904. Epub 2014 Jan 13.
Results Reference
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PubMed Identifier
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Citation
Weiser MR, Fichera A, Schrag D, Boughey JC, You YN. Progress in the PROSPECT trial: precision treatment for rectal cancer? Bull Am Coll Surg. 2015 Apr;100(4):51-2. No abstract available.
Results Reference
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Citation
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.
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Kang JH, Kim YC, Kim H, Kim YW, Hur H, Kim JS, Min BS, Kim H, Lim JS, Seong J, Keum KC, Kim NK. Tumor volume changes assessed by three-dimensional magnetic resonance volumetry in rectal cancer patients after preoperative chemoradiation: the impact of the volume reduction ratio on the prediction of pathologic complete response. Int J Radiat Oncol Biol Phys. 2010 Mar 15;76(4):1018-25. doi: 10.1016/j.ijrobp.2009.03.066. Epub 2009 Aug 3.
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Rouanet P. Which Trial to Demonstrate the Truthfulness of a Tailored Strategy in Rectal Carcinoma? Dis Colon Rectum. 2018 Jan;61(1):e1-e2. doi: 10.1097/DCR.0000000000000977. No abstract available.
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Nougaret S, Castan F, de Forges H, Vargas HA, Gallix B, Gourgou S, Rouanet P; GRECCAR Study Group. Early MRI predictors of disease-free survival in locally advanced rectal cancer from the GRECCAR 4 trial. Br J Surg. 2019 Oct;106(11):1530-1541. doi: 10.1002/bjs.11233. Epub 2019 Aug 22.
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Study Evaluating the Tailored Management of Locally-advanced Rectal Carcinoma

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