OncoMatch/Clinical Trials/NCT04215731
Neoadjuvant mFOLFOXIRI Plus Bevacizumab in Patients With High-Risk Locally Advanced Rectal Cancer
Is NCT04215731 recruiting? Yes, currently enrolling (May 2026). This Phase 3 trial studies multiple treatments including Neoadjuvant chemotherapy with mFOLFOXIRI plus bevacizumab and Induction chemotherpay with FOLFOX for rectal cancer.
Treatment: Neoadjuvant chemotherapy with mFOLFOXIRI plus bevacizumab · Induction chemotherpay with FOLFOX — Multimodality treatment that comprises preoperative fluoropyrimidine with concurrent radiotherapy followed by total mesorectal excision (TME) surgery and adjuvant fluoropyrimidine-based chemotherapy is recommended as a standard treatment of patients with stage II/III rectal cancer. However, the main target of radiotherapy is local control but no improvement in disease-free survival (DFS) or overall survival (OS) has been shown with this treatment strategy, which leaves approximately 30% of patients in whom distant metastases will develop. Moreover, the short- and long-term adverse effects of radiotherapy such as chronic pain, faecal incontinence and urogenital/anal dysfunction are associated with poor quality of life. Neadajuvant chemotherpay (NACT) alone has been proposed instead of preoperative chemoradiotherapy (CRT) with the aim of elimination of potential micrometastasis as early as possible while avoiding the adverse effects of radiotherapy, without jeopardizing local control. Evidence from the UK CR07 trial suggests that, without RT, a local recurrence rate of 5% (27/543) can be achieved if a complete mesorectal excision is carried out with a negative CRM. A small single-center phase II pilot trial treated patients with stage II or III rectal cancer with induction FOLFOX/bevacizumab chemotherapy followed by CRT only in those with stable or progressive disease and resection in all patients. All 32 of the participants had an R0 resection, and the 4-year DFS was 84%. Another phase II trial, which included 60 patients with stage II/III rectal cancer, assessed the R0 resection rate after FOLFOX plus either bevacizumab or cetuximab. An R0 resection was achieved in 98.3% of the participants, and the pathologic complete response rate was 16.7%. The phase III FOWARC trial, compared neoadjuvant therapy with and without radiation and found that perioperative mFOLFOX6 alone led to a similar downstaging rate as fluorouracil-radiotherapy, and no significant difference in outcomes was found between mFOLFOX6 without radiotherapy and 5-FU- radiotherapy. On the basis of the results of these trials, The investigators hypothesized that radiotherapy could be selectively omitted for patients who respond to NACT alone. The results of TRIBE showed that FOLFOXIRI plus bevacizumab yield a high objective response rate (ORR) (65%), early tumor shrinkage (ETS) (62.7%) and depth of response (DoR) (43.4%) in patients with metastatic colorectal cancer. The investigators were motivated to investigate this triplet-drugs chemotherpay plus bevacizumab both by the possibility of avoiding the toxicities of radiation without compromising local control, and the possibility that earlier introduction of intensive systemic therapy might achieve rapid tumor shrinkage, and improve distant control. The investigators conducted this phase III trial to compare neoadjuvant mFOLFOXIRI plus bevacizumab with selective radiotherapy with induction FOLFOX followed by concomitant chemoradiotherapy in patients with high-risk locally advanced rectal cancer.
Check if I qualifyExtracted eligibility criteria
Cancer type
Colorectal Cancer
Biomarker criteria
Excluded: MMR deficient
Diagnosis of dMMR or MSI-High tumor by immunohistochemistry or PCR testing
Excluded: MSH2 MSI-High
Diagnosis of dMMR or MSI-High tumor by immunohistochemistry or PCR testing
Disease stage
Required: Stage CT3 WITH MESORECTAL FASCIA INVOLVEMENT, CT4B, POSITIVE LATERAL LYMPH NODES (TNM)
Evaluated by pelvic contrast-enhanced MRI as having high-risk locally advanced disease: cT3 with mesorectal fascia involvement, or cT4a/b, or positive lateral lymph nodes (TNM staging reference provided). Evidence of distant metastasis (M1) confirmed by systemic CT, MRI, or PET-CT (at minimum including chest, abdomen, and pelvis) [excluded].
Performance status
ECOG 0–1(Restricted strenuous activity)
Prior therapy
Cannot have received: systemic anti-cancer therapy
No prior systemic anti-cancer therapy for colorectal cancer, including cytotoxic drugs, immune checkpoint inhibitors, molecular targeted therapy, or endocrine therapy
Cannot have received: pelvic radiotherapy
Prior pelvic radiotherapy, or any anti-cancer therapy (chemotherapy, targeted therapy, hormonal therapy, immunotherapy, biologic therapy, etc.) within 12 months prior to enrollment
Cannot have received: anti-cancer therapy
any anti-cancer therapy (chemotherapy, targeted therapy, hormonal therapy, immunotherapy, biologic therapy, etc.) within 12 months prior to enrollment
Lab requirements
Blood counts
Adequate bone marrow function as assessed by laboratory requirements conducted within 7 days of starting study treatment
Kidney function
Adequate renal function as assessed by laboratory requirements conducted within 7 days of starting study treatment
Liver function
Adequate hepatic function as assessed by laboratory requirements conducted within 7 days of starting study treatment
Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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