mFOLFOXIRI Plus Bevacizumab for Organ Preservation in Locally Advanced Rectal Cancer (FOBEAR-ii)

Neoadjuvant mFOLFOXIRI Plus Bevacizumab for Organ Preservation in Locally Advanced Rectal Cancer: A Singe-arm Phase II Study

Neoadjuvant mFOLFOXIRI plus bevacizumab may achieve tumor shrinkage and reduce micrometastases, offering a radiotherapy-free organ-preservation alternative for locally advanced rectal cancer. This phase II trial will enroll patients with stage II-III rectal cancer to receive six cycles of neoadjuvant mFOLFOXIRI plus bevacizumab, followed by watch-and-wait, local excision, or total mesorectal excision based on response.

Study Overview

• Status: Not yet recruiting
• Conditions: Phase 2 Study
• Intervention / Treatment: Drug: FOLFOXIRI + Bevacizumab

Detailed Description

Wait and watch following neoadjuvant chemoradiotherapy is a effective organ preservation strategy in locally advanced rectal cancer. However, radiotherapy is associated with significant pelvic organ toxicity and does not reduce the risk of distant metastasis. Neoadjuvant mFOLFOXIRI plus bevacizumab can achieve effective tumor shrinkage and might simultaneously reduce micrometastatic disease. On this basis, we here propose an active organ-preservation strategy using neoadjuvant mFOLFOXIRI plus bevacizumab in locally advanced rectal cancer. This multicenter, single-arm, phase II trial will enroll patients with stage II-III rectal cancer to receive six cycles of neoadjuvant mFOLFOXIRI plus bevacizumab. Based on clinical response after treatment, patients will undergo watch-and-wait, local excision, or total mesorectal excision. Post-treatment surveillance will combine imaging with tumor-informed circulating tumor DNA (ctDNA) monitoring. The primary endpoint is the 3-year disease-free survival rate. This study is expected to provide clinical evidence on the safety and efficacy of a radiotherapy-free active watch-and-wait strategy for rectal cancer.

• Study Type: Interventional
• Enrollment (Estimated): 119
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zerong Cai, M.D.; Phone Number: 86-020-38455325; Email: caizer@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Sign the informed consent form and comply with the planned visits, study treatment, laboratory tests, and other trial procedures;
• Age 18-75 years;
• Histologically confirmed rectal adenocarcinoma;
• The lower edge of the rectal tumor is <10 cm from the anal verge (as assessed by pelvic MRI);
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
• Willing to choose the "organ preservation" strategy according to the study protocol;
• Locally staged as cTNM stage II-III (T3-4 with any N, or any T with N1-2) by contrast-enhanced pelvic MRI;
• No prior antitumor therapy for colorectal cancer, including cytotoxic drugs, radiotherapy, molecular targeted therapy, immune checkpoint inhibitors, etc.;
• Adequate organ function as indicated by the following laboratory values obtained during the screening period: white blood cell count ≥3×10⁹/L, neutrophil count ≥1.5×10⁹/L, platelet count ≥75×10⁹/L, serum total bilirubin ≤1.5× upper limit of normal (ULN), aspartate aminotransferase or alanine aminotransferase ≤2.5× ULN, serum creatinine ≤1.5× ULN.

Exclusion Criteria:

• Distant metastasis (M1) confirmed by chest/abdominal/pelvic CT, pelvic MRI, or PET-CT;
• Bowel obstruction, active gastrointestinal bleeding, or perforation caused by the tumor;
• Tumor complicated by intestinal fistula or pelvic abscess;
• Concurrent malignant tumors of other organ systems (except malignancies that have been curatively treated with no recurrence for more than 5 years, or carcinoma in situ that can be cured by adequate treatment);
• Thrombotic or embolic events within 12 months prior to enrollment, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, or deep vein thrombosis;
• Within 12 months prior to enrollment, any of the following: myocardial infarction, severe/unstable angina, New York Heart Association (NYHA) class ≥ II cardiac dysfunction, clinically significant supraventricular or ventricular arrhythmia, and symptomatic congestive heart failure;
• Tumors diagnosed as mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) by immunohistochemistry or PCR;
• Uncontrolled systemic infection or unexplained fever (>38.5°C) within 2 weeks prior to enrollment;
• Concurrent presence of any of the following other diseases: human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness; poorly controlled diseases including but not limited to non-infectious pneumonitis, diabetes mellitus, hypertension, pulmonary fibrosis, acute pneumonia, aneurysm, and coagulation disorders; or any other disease that, in the investigator's opinion, may affect the assessment of study endpoints;
• Known or suspected allergy to the study drugs;
• Pregnant or lactating women;
• Patients with other serious physical or mental illnesses or laboratory abnormalities that may increase the risk of study participation, interfere with study results, or who are considered unsuitable for participation by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FOLFOXIRI+BEVA; Patients will receive neoadjuvant mFOLFOXIRI plus bevacizumab for 6 cycles, with 14 days per cycle.	Drug: FOLFOXIRI + Bevacizumab; Oxaliplatin 85 mg/m² intravenous infusion over 180 minutes on day 1; irinotecan 150 mg/m² intravenous infusion over 90 minutes on day 1; leucovorin 400 mg/m² intravenous infusion over 120 minutes on day 1; 5-fluorouracil 2400 mg/m² continuous intravenous infusion over 46 hours; bevacizumab 5 mg/kg intravenous infusion over 30-90 minutes on day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
3-year Disease Free Survival	From the enrollment to 3 years following enrollment

Collaborators and Investigators

• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2031

Study Registration Dates

• First Submitted: September 8, 2026
• First Submitted That Met QC Criteria: September 8, 2026
• First Posted (Actual): September 14, 2026

Study Record Updates

• Last Update Posted (Actual): September 14, 2026
• Last Update Submitted That Met QC Criteria: September 8, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: BEVACIZUMAB; FOLFOXIRI; ORGAN PRESERVATION; RECTAL CANCER
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab
• Other Study ID Numbers: 2026ZSLYEC-671

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No