CapeOX Combined With Bevacizumab Plus Anti-PD1 Antibody as Neoadjuvant Therapy for Locally Recurrent Colorectal Cancer

This prospective, single-arm study aims to investigate the efficacy and safety of CapeOX combined with Bevacizumab plus Anti-PD1 Antibody as neoadjuvant therapy for locally recurrent colorectal cancer

Study Overview

• Status: Recruiting
• Conditions: Locally Recurrent Colorectal Cancer
• Intervention / Treatment: Drug: Capecitabine; Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Haiyang Zhou, MD; Phone Number: +86 81885615; Email: haiyang1985_1@aliyun.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Changzheng Hospital
    • Contact: Haiyang Zhou, MD; Phone Number: +86 81885615; Email: haiyang1985_1@aliyun.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Primary colorectal cancer underwent radical surgery, histologically confirmed as adenocarcinoma and achieved R0 resection, and postoperative adjuvant chemotherapy with Xelox or other first-line standard regimens.
• Based on the imaging and histological examination results, the patient was clinically assessed and diagnosed with locally recurrent colorectal adenocarcinoma.
• The patients did not receive any treatment, including chemotherapy, targeted therapy, immunotherapy, or radiotherapy, within the past month.
• Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) 0-1.
• Absence of distant metastasis confirmed by CT, MRI or PET/CT.
• Adequate hematologic and organ function, defined by protocol-specified laboratory test results, obtained within 7 days before first dose. Absolute neutrophil count ≥1500/mm3, platelet ≥100,000/mm3, Hb ≥10g/dl, serum creatinine ≤1.5 times ULN, creatinine clearance rate ≥50mL/min, ALT and AST ≤2.5 times ULN, INR or aPTT ≤1.5 times ULN (INR ≤2 times ULN and aPTT in normal range for patients who are on prophylactic anticoagulant therapy within 14 days before study treatment), total bilirubin level ≤2 times ULN (within 7 days before study treatment).
• Women of childbearing age should confirm that serum pregnancy test is negative and agree to use effective contraceptive methods during study treatment and the following 60 days.
• Life expectancy> 3 months
• Signed and written informed consent

Exclusion Criteria:

• Previously received anti-PD1 or anti-PDL1 or anti-PDL2 or anti-CTLA4.
• Intestinal obstruction or uncontrollable active bleeding caused by the tumor requiring urgent treatment.
• Contraindications of Oxaliplatin, Capecitabine, Bevacizumab, and Tislelizumab.
• Hypersensitivity to other monoclonal antibodies.
• Any active, known or suspected autoimmune disease.
• Uncontrolled pleural effusion, pericardial effusion, or ascites to a moderate or greater extent.
• History of one of the following diseases: idiopathic pulmonary fibrosis, organized pneumonia (eg. bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia and interstitial pneumonia, or evidence of active pneumonia through enhanced chest CT screening.
• Major surgery within 4 weeks before enrollment and haven't fully recovered from the previous surgery.
• Active bleeding or abnormal coagulation (aPTT >43s or INR >1.5 times ULN), or having a tendency to bleed or receiving thrombolytic or anticoagulant therapy.
• Previously received allogeneic stem cell or parenchymal organ transplantation.
• Any significant clinical or laboratory abnormality that the investigator considers to influence the safety assessment, eg. uncontrolled active infection, uncontrolled diabetes, hypertension that cannot be reduced to normal range with monotherapy, grade II or above peripheral neuropathy, congestive heart failure, heart disease (class II or higher) as defined by the New York College of Cardiology, myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, unstable angina pectinis, chronic kidney disease, abnormal thyroid function and previous or co-existing malignancies.
• History of uncorrected serum electrolyte disturbances such as potassium, calcium and magnesium.
• HIV infection.
• Active hepatitis B or hepatitis C.
• Pregnancy or lactation period, or unwilling to use contraception during the trial.
• With other malignancy within 5 year, except cervical carcinoma in situ, basal or squamous skin cancer, local prostatic carcinoma and ductal carcinoma in situ.
• Use corticosteroids (dose of prednisone or similar drugs> 10mg/day) or other immunosuppressive agents within 14 days before enrollment.
• Patients with active tuberculosis (TB) who are receiving anti-TB treatment or have received anti-TB treatment within 1 year.
• Active infection, or treatment with oral or intravenous antibiotics within the first 2 weeks prior to neoadjuvant therapy, except prophylactic administration.
• Anti-infective vaccine (eg. influenza vaccine, varicella vaccine, etc.) injection within 4 weeks before neoadjuvant therapy.
• Previous participation in other clinical trials within 4 weeks before neoadjuvant therapy.
• Any other disease, metabolic disorder, abnormal physical examination or abnormal laboratory results that may constrain the use of trial drug, or affect the reliability of study results, or lead to high risk of treatment complications, or affect patient compliance.

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: CapeOx+ Bevacizumab + Tislelizumab as neoadjuvant treatment; CapeOx: Capecitabine is given orally at 1000mg / m² twice a day from day1-14 every 3 weeks for 4 cycles and Oxaliplatin is given by intravenous infusion at 130mg / m² on Day 1 every 3 weeks for 4 cycles; Bevacizumab：Bevacizumab is given intravenously at 7.5mg/kg on day 1 every 3 weeks for 4 cycles; Tislelizumab：Tislelizumab is given intravenously at 200 mg on day 1 every 3 weeks for 4 cycles

Drug: Capecitabine; Capecitabine is given orally at 1000mg / m² twice a day from day1-14 every 3 weeks for 4 cycles; Drug: Oxaliplatin; Oxaliplatin is given by intravenous infusion at 130mg / m² on Day 1 every 3 weeks for 4 cycles; Drug: Bevacizumab; Bevacizumab is given intravenously at 7.5mg/kg on day 1 every 3 weeks for 4 cycles; Drug: Tislelizumab; Tislelizumab is given intravenously at 200 mg on day 1 every 3 weeks for 4 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	Percentage of patients who achieve R0 resection	15 weeks
Pathological complete response rate	Percentage of patients who achieve pathological complete response (pCR) based on local investigator	15 weeks
Tumor regression grade (TRG)		15 weeks
Incidence of Treatment-Related Adverse Events	Number of adverse events	Until 30 days after the last treatment
Objective response rate	Percentage of patients who achieve partial response (PR) or complete response (CR)	15 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event free survival	Measure of time from study treatment to disease progression or death	Up to 3 years
Disease-free survival	Measure of time from the date of surgery to disease relapse or death	Up to 3 years
One-year or two-year disease-free survival rate	Percentage of patients who achieve disease-free survival lasting for more than one and two years respectively from the date of surgery	Up to 2 years
One-year or two-year overall survival rate	Percentage of patients who achieve survival for more than one and two years respectively from date of first dose	Up to 2 years
Quality of life score (QoL score)	Assessment of life quality based on EORTC QLQ-C30	Until 30 days after the last treatment
Surgical complications		Until 90 days after surgery

Collaborators and Investigators

• Sponsor: Shanghai Changzheng Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: March 12, 2025
• First Submitted That Met QC Criteria: March 12, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 12, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Recurrence; Colorectal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Capecitabine; Oxaliplatin; Bevacizumab; Tislelizumab
• Other Study ID Numbers: ZHOUHAIYANG4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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