A phase III randomized trial evaluating chemotherapy followed by pelvic reirradiation versus chemotherapy alone as pre-operative treatment for locally recurrent rectal cancer (GRECCAR – PRODIGE – FRENCH) - GRECCAR 15

2024-514705-62-00 Protocol CHUBX 2017/52 Therapeutic confirmatory (Phase III) Ongoing, recruitment ended

Start 8 Jul 2019 · Status Ongoing, recruitment ended · 1 EU/EEA countries · 22 sites · Protocol CHUBX 2017/52

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruitment ended
Participants planned 186
Countries 1
Sites 22

Recurrent rectal cancer after local excision

To assess the efficacy of neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone on the rate of curative surgery (R0) in previously irradiated patients with LRRC

Key facts

Sponsor
Centre Hospitalier Universitaire De Bordeaux
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Neoplasms [C04]
Trial duration
8 Jul 2019 → ongoing
Decision date (initial)
2024-07-04
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Ministry for Health and Solidarity, France, DGOS/PHRC-K

External identifiers

EU CT number
2024-514705-62-00
EudraCT number
2018-002833-39
ClinicalTrials.gov
NCT03879109

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To assess the efficacy of neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone on the rate of curative surgery (R0) in previously irradiated patients with LRRC

Secondary objectives 6

  1. To compare neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone on 3-year Disease Free Survival and 3-year Overall Survival
  2. To compare neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone on Surgical morbidity and mortality (Dindo classification) at 30 days
  3. To compare neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone on Compliance to the neoadjuvant treatment
  4. To compare neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone on Good tumor response
  5. To compare neoadjuvant chemotherapy followed by pelvic reirradiation versus neoadjuvant chemotherapy alone on Quality of life at two years after surgery
  6. To assess the toxicity of neoadjuvant treatment

Conditions and MedDRA coding

Recurrent rectal cancer after local excision

VersionLevelCodeTermSystem organ class
20.0 PT 10038038 Rectal cancer 100000004864

Study design 2 periods

#TitleAllocationBlindingRoles blindedArms
1 Arm A (experimental): Induction Chemotherapy followed by pelvic reirradiation
Protocol of chemotherapy FOLFIRINOX*, 4 or 6 cycles : - oxaliplatin: 85 mg/m2 - irinotecan: 180 mg/m² - folinic acid: 400 mg/m2 - 5FU : 400 mg/m2 (bolus) - 5FU : 2400 mg/m2 (continuous infusion) Protocol of reirradiation consists in conformational intensity modulated external irradiation, delivering a 30.6 Gy dose (1.8 Gy/day), with concomitant chemotherapy including Capecitabine 1600 mg/m²/day, five days a week.
 Randomised Controlled None Arm A (experimental): Induction Chemotherapy followed by pelvic reirradiation
2 Arm B (Control): Chemotherapy alone
Protocol of chemotherapy FOLFIRINOX*, 4 or 6 cycles : - oxaliplatin: 85 mg/m2 - irinotecan: 180 mg/m² - folinic acid: 400 mg/m2 - 5FU : 400 mg/m2 (bolus) - 5FU : 2400 mg/m2 (continuous infusion)
 Randomised Controlled None Arm B (Control): Chemotherapy alone

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

  1. Signed and dated informed consent
  2. Age ≥ 18 years
  3. First or second LRRC (histologically proven) ≤ 15 cm from the anal verge
  4. Previous pelvic irradiation for the primary rectal cancer or primary recurrence (25-50.4Gy)
  5. No distant metastasis
  6. Resectable locally recurrent rectal cancer (according to the International consensus, absolute contraindications for resectabililty are bilateral sciatic nerve involvement, circumferential bone involvement, high sacral involvement requiring total sacrectomy; relative contraindications for resectabilty are sciatic notch involvement and encasement external iliac vessels)
  7. Adequate hematologic function : Hemoglobin ≥ 9 g/dL, neutrophil count ≥ 1500/mm3, blood platelets ≥ 100 000/mm3
  8. Adequate hepatic function : total bilirubin ≤ 1,5 x ULN, ASAT et ALAT ≤ 3 x ULN, alkalin phosphatases ≤ 3 x ULN
  9. Adequate renal function : creatinine clearance ≥ 30 ml/min
  10. ECOG performance status < 2
  11. Women not sterilized by the first treatment (ovarian transposition) and males (and their female partners) patients agree to use two methods of effective contraception (one of them being a barrier method) during the study, for at least 6 months for men and for women after the last administration of study treatment
  12. Patient affiliated to a social security system or beneficiary of the same
  13. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion criteria 15

  1. Recurrent rectal cancer after local excision
  2. Concomitant cancer or medical history of cancer (other than that of rectal disease) within 5 years other than cancers treated in situ (cervical carcinoma or basocellular carcinoma or spinocellular carcinoma)
  3. Contraindication for chemotherapy (refer to Summary of characteristics of the products of the study drugs available at http://base-donnees-publique.medicaments.gouv.fr) or radiotherapy or surgery
  4. Symptomatic cardiac or coronary insufficiency
  5. Personal or family history of long QT syndrome congenital
  6. ECG at screening or baseline (predose) with QT/QTc > 450 msec (male) or QT/QTc > 470 msec (female)
  7. Chronic inflammatory bowel disease and/or bowel obstruction, digestive abscess or fistula
  8. Patients with hypocalcemia, hypokalemia, hypomagnesemia
  9. Progressive active infection (HIV or chronic hepatitis B or C) or any other severe medical condition that may preclude the delivery of treatment
  10. Complete or partial Dihydropyrimidine deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)
  11. If contraindication to FOLFIRINOX, possibility to administred FOLFOX or FOLFIRI +/-EGFR (Contraindication to oxaliplatin: peripheral neuropathy > grade 1 (CTCAE grading system v5.0))
  12. Concomitant treatment with millepertuis, yellow fever vaccine, live attenuated vaccine, phenytoin, warfarin or sorivudine (or chemically equivalent)
  13. Pregnant or breast-feeding woman
  14. Persons deprived of liberty or under guardianship or incapable of giving consent
  15. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up schedule, as assessed by investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Proportion of curative surgery (R0 resection)

Secondary endpoints 6

  1. 3-year Disease Free and 3-year Overall Survival
  2. Surgical morbidity and mortality (Dindo classification) during first 30 days after the surgery
  3. Compliance to treatment: proportion of patients receiving full allocated neoadjuvant treatment
  4. Proportion of good tumor response: LRRC with a decreasing size of 50% after preoperative treatment (defined as good MRI radiological responders according to previous data in the literature)
  5. Proportion of treatment related toxicity using International Common Terminology Criteria for Adverse Events (CTCAE) grading system v5.0
  6. Quality of life (QLQ-C30 and QLQ-CR29) before neoadjuvant treatment, before surgery, 6 months, one year and two years after surgery

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

CAMPTO 20 mg/mL, solution à diluer pour perfusion (IV)

PRD495174 · Product

Active substance
Irinotecan Hydrochloride Trihydrate
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS USE
Max daily dose
180 mg/m2 milligram(s)/sq. meter
Max total dose
1080 mg/m2 milligram(s)/square meter
Max treatment duration
12 Week(s)
Authorisation status
Authorised
ATC code
L01CE02 — -
Marketing authorisation
34009 572 690 2 9
MA holder
PFIZER HOLDING FRANCE
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

ELOXATINE 5 mg/ml, solution à diluer pour perfusion

PRD482013 · Product

Active substance
Oxaliplatin
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS USE
Max daily dose
85 mg/m2 milligram(s)/square meter
Max total dose
510 mg/m2 milligram(s)/square meter
Max treatment duration
12 Week(s)
Authorisation status
Authorised
ATC code
L01XA03 — OXALIPLATIN
Marketing authorisation
34009 565 983 8 0
MA holder
SANOFI WINTHROP INDUSTRIE
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Xeloda 150 mg film-coated tablets

PRD9863933 · Product

Active substance
Capecitabine
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
1600 mg/m2 milligram(s)/sq. meter
Max total dose
27200 mg/m2 milligram(s)/square meter
Max treatment duration
17 Day(s)
Authorisation status
Authorised
ATC code
L01BC06 — CAPECITABINE
Marketing authorisation
EU/1/00/163/001
MA holder
CHEPLAPHARM ARZNEIMITTEL GMBH
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

ELVORINE 100 mg/10 mL, solution injectable

PRD422519 · Product

Active substance
Levoleucovorin
Substance synonyms
Levofolinic acid, L-Folinic acid
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS USE
Max daily dose
400 mg/m2 milligram(s)/square meter
Max total dose
2400 mg/m2 milligram(s)/square meter
Max treatment duration
12 Week(s)
Authorisation status
Authorised
ATC code
V03AF04 — CALCIUM LEVOFOLINATE
Marketing authorisation
34009 348 990 6 5
MA holder
PFIZER HOLDING FRANCE
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

FLUOROURACILE ACCORD 50 mg/ml, solution à diluer pour perfusion

PRD415414 · Product

Active substance
Fluorouracil
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS USE
Max daily dose
1200 mg/m2 milligram(s)/square meter
Max total dose
14400 mg/m2 milligram(s)/square meter
Max treatment duration
12 Week(s)
Authorisation status
Authorised
ATC code
L01BC02 — FLUOROURACIL
Marketing authorisation
34009 575 179 7 7
MA holder
ACCORD HEALTHCARE FRANCE SAS
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Bordeaux

27 Total trials 14 Recruiting 6 Ended
Academic / Non-commercial
Sponsor organisation
Centre Hospitalier Universitaire De Bordeaux
Address
12 Rue Dubernat, Cs 91286 Cs 91286
City
Talence
Postcode
33400
Country
France

Scientific contact point

Organisation
Centre Hospitalier Universitaire De Bordeaux
Contact name
Coordinating Investigator

Public contact point

Organisation
Centre Hospitalier Universitaire De Bordeaux
Contact name
Coordinating Investigator

Locations

1 EU/EEA country · 22 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ongoing, recruitment ended 186 22
Rest of world — 0 —

Investigational sites

France

22 sites · Ongoing, recruitment ended
Hospices Civils De Lyon
Chirurgie Digestive, 165 Chemin Du Grand Revoyet, 69310, Pierre Benite
Centre Oscar Lambret
Chirurgie Digestive, 3 Rue Frederic Combemale, 59000, Lille
Assistance Publique Hopitaux De Paris
Cancérologie-Radiothérapie, 1 Avenue Claude Vellefaux, 75010, Paris
Centre Hospitalier Universitaire De Rennes
Chirurgie Digestive, 2 Rue Henri Le Guilloux, 35000, Rennes
Institut De Cancerologie De L Ouest
Chirurgie Digestive, Boulevard Jacques Monod, 44805, Saint-Herblain Cedex
Centre Henri Becquerel
Radiothérapie, Rue D Amiens, 76038, Rouen Cedex
Centre Leon Berard
Chirurgie Digestive, 28 Rue Laennec, 69008, Lyon
Assistance Publique Hopitaux De Paris
Chirurgie Digestive, 100 Boulevard Du General Leclerc, 92110, Clichy
Assistance Publique Hopitaux De Paris
Chirurgie Digestive, 184 Rue Du Faubourg Saint Antoine, 75012, Paris
Assistance Publique Hopitaux De Paris
Chirurgie générale et digestive, 78 Rue Du General Leclerc, 94270, Le Kremlin-Bicetre
GIE Groupe hospitalier Paris Saint-Joseph/Vinci
Chirurgie Digestive et Obésité, 185 Rue Raymond Losserand, 75674, Paris Cedex 14
CHRU De Nancy
Chirurgie Digestive hépatobiliaire, endocrinienne et cancérologique, 11 Rue Du Morvan, Bp 80001, Vandoeuvre Les Nancy Cedex
Institut Paoli Calmettes
Chirurgie Digestive, 232 Boulevard De Sainte Marguerite, Bp 156, Marseille
Institut Regional Du Cancer De Montpellier
Chirurgie Digestive, 208 Avenue Des Apothicaires, 34298, Montpellier Cedex 5
Besancon University Hospital Center
Chirurgie Digestive, 2 Place Saint Jacques, Cs 51804, Besancon Cedex
Sainte Catherine Institut Du Cancer Avignon-Provence
Unité Fonctionnelle Onco-Digestif, 250 Chemin De Baigne Pieds, 84918, Avignon Cedex 9
Centre Hospitalier Universitaire De Bordeaux
Chirurgie digestive et endocrinienne, Avenue De Magellan, 33600, Pessac
Centre Hospitalier Universitaire Grenoble Alpes
Chirurgie Digestive, Boulevard De La Chantourne, 38700, La Tronche
Assistance Publique Hopitaux De Paris
Chirurgie Digestive, 20 Rue Leblanc, 75015, Paris
Centre Hospitalier Universitaire De Toulouse
Chirurgie Digestive, 1 Avenue Du Professeur Jean Poulhes, Tsa 50032, Toulouse Cedex 9
Centre Hospitalier Universitaire Rouen
Chirurgie Digestive, 1 Rue De Germont, Bp 96031, Rouen Cedex
Institut Universitaire Du Cancer Toulouse-Oncopole
Radiothérapie, 1 Avenue Irene Joliot Curie, 31059, Toulouse Cedex 9

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2019-07-08 2019-07-08 2022-11-07

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-06-11 France Acceptable
2024-06-26
 2024-07-04

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