Chemotherapy Followed by Pelvic Reirradiation Versus Chemotherapy Alone as Pre-operative Treatment for Locally Recurrent Rectal Cancer

NCT03879109 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: CHUBX 2017/52
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 13

Brief Summary

GRECCAR 15 is focused on Locally Recurrent Rectal Cancer (LRRC) for patients with previous pelvic radiotherapy for the primary rectal cancer. This situation leads to a 20% higher risk of non-curative resection for the LRRC management (R1 status) impacting significantly the overall survival. The widespread use of neoadjuvant radiotherapy for primary rectal cancer introduces this new problem: the treatment of LRRC in previously irradiated area. The objective of GRECCAR 15 is 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.

Conditions

Rectal Cancer

Keywords

Locally recurrent rectal cancer; Pelvic reirradiation; Oncological surgery

Outcome Measures

Primary Outcomes (1)

• Proportion of curative surgery

  To determine the rate of R0 resection

  At surgery, expected average 6 to 8 weeks after neoadjuvant treatment

Secondary Outcomes (9)

• Disease Free Survival

  From surgery until 3 years of follow-up

• Overall Survival

  From surgery until 3 years of follow-up

• Surgical morbidity

  From surgery until 30 days after surgery

• Surgical mortality

  From surgery until 30 days after surgery

• Compliance to treatment

  From beginning of neoadjuvant treatment until surgery, expected average 20 weeks after neoadjuvant treatment

Study Arms (2)

Arm A: Induction Chemotherapy followed by Pelvic reirradiation

EXPERIMENTAL

Protocol of chemotherapy FOLFIRINOX\*, 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.

Drug: Chemotherapy FOLFIRINOX, 6 cycles; Radiation: Radiochemotherapy; Procedure: Surgery

Arm B: Chemotherapy alone

ACTIVE COMPARATOR

Protocol of chemotherapy FOLFIRINOX\*, 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)

Drug: Chemotherapy FOLFIRINOX, 6 cycles; Procedure: Surgery

Interventions

Chemotherapy FOLFIRINOX, 6 cycles DRUG

* oxaliplatin: 85 mg/m2 * irinotecan: 180 mg/m² * folinic acid: 400 mg/m2 * 5FU : 400 mg/m2 (bolus) * 5FU : 2400 mg/m2 (continuous infusion)

Arm A: Induction Chemotherapy followed by Pelvic reirradiation; Arm B: Chemotherapy alone

Radiochemotherapy RADIATION

Reirradiation consists in conformational intensity modulated external irradiation (Intensity-modulated radiotherapy Volumetric Modulated Arc Therapy or tomotherapy) delivering a 30.6 Gy dose with high-energy photons in fractions of 1.8 Gy per day (17 fractions) 5 days a week With Concomitant chemotherapy including Capecitabine 1600 mg/m²/day, five days a week.

Arm A: Induction Chemotherapy followed by Pelvic reirradiation

Surgery PROCEDURE

Surgery will be performed at: * Arm A: 8 weeks (±1) after the end of treatment * Arm B: 6 weeks (±1) after the end of treatment Surgical procedures are defined into three categories: * Total mesorectal excision (TME) * Extended-TEM (e-TME) * Pelvic exenteration (PE)

Arm A: Induction Chemotherapy followed by Pelvic reirradiation; Arm B: Chemotherapy alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent
• Age ≥18 years
• LRRC (histologically proven) ≤ 15 cm from the anal verge
• First or second LRRC (histologically proven) ≤ 15 cm from the anal verge
• Previous pelvic irradiation for the primary rectal cancer or primary recurrence (25-50.4Gy)
• No distant metastasis
• 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)
• Adequate hematologic function : Hemoglobin ≥ 9 g/dL, leukocytes ≥ 4000/mm3, neutrophil count ≥ 1500/mm3, blood platelets ≥ 100 000/mm3
• Adequate hepatic function : total bilirubin ≤ 1,5 x ULN, ASAT et ALAT ≤ 3 x ULN, alkalin phosphatases ≤ 3 x ULN
• Adequate renal function : creatinine clearance ≥ 30 ml/min
• ECOG performance status \< 2
• 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
• Patient affiliated to a social security system or beneficiary of the same
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

You may not qualify if:

• Recurrent rectal cancer after local excision
• Concomitant cancer or medical history of cancer within 5 years other than cancers treated in situ (cervical carcinoma or basocellular carcinoma or spinocellular carcinoma)
• Contraindication for chemotherapy 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
• Symptomatic cardiac or coronary insufficiency
• Personal or family history of long QT syndrome congenital
• ECG at screening or baseline (predose) with QT/QTc \> 450 msec (male) or QT/QTc \> 470 msec (female)
• Chronic inflammatory bowel disease and/or bowel obstruction
• Patients with hypocalcemia, hypokalemia, hypomagnesemia.
• Progressive active infection (HIV or chronic hepatitis B or C) or any other severe medical condition that may preclude the delivery of treatment
• Complete or partial Dihydropyrimidine deshydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)
• If contraindication to FOLFIRINOX, possibility to administred FOLFOX or FOLFIRI +/-EGFR (Contraindication to oxaliplatin: peripheral neuropathy \> grade 1 (CTCAE grading system v5.0)
• Peripheral neuropathy \> grade 1 (CTCAE grading system v5.0)
• Concomitant treatment with millepertuis, yellow fever vaccine, live attenuated vaccine, phenytoin, warfarin or sorivudine (or chemically equivalent)
• Pregnant or breast-feeding woman
• Persons deprived of liberty or under guardianship or incapable of giving consent

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (13)

Institut Sainte Catherine

Avignon, France

Location

CHU Bordeaux

Bordeaux, France

Location

CHU Grenoble

Grenoble, France

Location

Centre Oscar Lambret

Lille, France

Location

Hospices Civils de Lyon, HCL

Lyon, France

Location

Institut Paoli Calmette

Marseille, France

Location

Institut du Cancer de Montpellier

Montpellier, France

Location

CHRU Nancy

Nancy, France

Location

Groupe Hospitalier Paris Saint-Joseph

Paris, France

Location

CHU Rennes

Rennes, France

Location

CHU Rouen

Rouen, France

Location

Institut de Cancérologie de l'Ouest

Saint-Herblain, France

Location

CHU Toulouse

Toulouse, France

Location

Related Publications (1)

• Denost Q, Frison E, Salut C, Sitta R, Rullier A, Harji D, Maillou-Martinaud H, Rullier E, Smith D, Vendrely V; on behalf the GRECCAR Group. A phase III randomized trial evaluating chemotherapy followed by pelvic reirradiation versus chemotherapy alone as preoperative treatment for locally recurrent rectal cancer - GRECCAR 15 trial protocol. Colorectal Dis. 2021 Jul;23(7):1909-1918. doi: 10.1111/codi.15670. Epub 2021 Jun 10.

  PMID: 33843133 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Chemoradiotherapy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Study Officials

• Christophe LAURENT

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2019
• First Posted: March 18, 2019
• Study Start: July 8, 2019
• Primary Completion: June 30, 2024
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 14, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (13)