Brouquet 2020 - GRECCAR16 Trial Protocol

Full citation: Brouquet A, Bachet JB, Huguet F, Karoui M, Artru P, Sabbagh C, Lefèvre JH, Vernerey D, Mariette C, Vicaut E, Benoist S, on behalf of the FRENCH, GRECCAR, PRODIGE study groups. NORAD01-GRECCAR16 multicenter phase III non-inferiority randomized trial comparing preoperative modified FOLFIRINOX without irradiation to radiochemotherapy for resectable locally advanced rectal cancer (intergroup FRENCH-GRECCAR-PRODIGE trial). BMC Cancer. 2020;20:485. ClinicalTrials.gov NCT03875781.

Raw PDF: raw/Brouquet 2020 - GRECCAR16 Trial Protocol.pdf

Study type / design

This is a study protocol paper, not a results paper — it describes trial design only; no efficacy or safety outcomes are reported (or yet available at time of this wiki’s ingest). Phase III, multicenter (40 French centers), open-label, randomized, 2-arm, non-inferiority trial. Patients with resectable locally advanced rectal cancer (LARC) — mid/low rectal, cT3N0 or cT1-T3N+ with predictive circumferential resection margin (CRM) >2mm on pretreatment MRI — are randomized 1:1 to:

• Experimental arm: 6 cycles of preoperative modified FOLFIRINOX (no pelvic irradiation), then MRI reassessment, then TME surgery.
• Control arm: standard radiochemotherapy (Cap50: 50 Gy/25 fractions IMRT + concurrent capecitabine), then MRI reassessment, then TME surgery.

Target enrollment 574 patients. Primary endpoint: 3-year progression-free survival (a modified definition — a CRM ≤2mm on post-treatment MRI reassessment counts as a progression event, to guard against loss of oncologic control from omitting radiotherapy). Key secondary endpoints: R0 resection rate, sphincter-preservation rate, loco-regional recurrence-free survival, overall survival, bowel/ sexual function (LARS score, EORTC QLQ-CR29), quality of life.

Rationale (per the protocol’s own framing)

This trial tests radiation omission via full-dose systemic chemotherapy alone, not TNT intensification — a different question from RAPIDO/PRODIGE 23/STELLAR (which test adding systemic therapy to standard CRT/SCRT). The rationale: standard preoperative RCT has never been shown to reduce metastatic recurrence or improve OS, and carries meaningful late toxicity risk (fecal incontinence up to 62% vs 38% without RT; severe LARS 56% vs 35%; sexual dysfunction) — the protocol argues selected CRM-negative patients on MRI may not need pelvic irradiation at all if full-dose oxaliplatin/irinotecan-based chemotherapy alone can achieve comparable local control. Distinct from Schrag 2023 - PROSPECT Trial, which uses selective CRT only for poor responders to FOLFOX rather than omitting radiotherapy for all patients upfront.

Status as of this ingest

No results available — this is the trial design publication only (2020). The wiki’s Total Neoadjuvant Therapy (TNT) and Rectal Cancer pages previously referenced GRECCAR16 (as “NORAD01-GRECCAR16”) only as an ongoing trial per PRODIGE 23’s long-term discussion section — this source page now grounds that reference in the actual protocol rather than a secondhand mention, but efficacy data remains unavailable pending trial completion/publication.

Limitations

• Protocol paper only — no outcomes to assess.
• Non-inferiority design with a fairly permissive margin (true HR up to 1.34 still allows declaring non-inferiority) — worth noting when results are eventually ingested, since non-inferiority claims are sensitive to margin choice.
• Postoperative treatment is not standardized (left to local multidisciplinary team discretion per French guidelines) — a source of between-center variability the eventual results paper will need to address.

Relevance

Updates this wiki’s prior “ongoing, worth checking for results” note on NORAD01-GRECCAR16 (see Total Neoadjuvant Therapy (TNT) Open items) with actual protocol detail — trial design, primary endpoint, and rationale are now documented, but the substantive question (is chemotherapy-alone non-inferior to CRT for CRM-negative LARC) remains open pending a future results publication.