CapeOX Combined With Bevacizumab Plus Anti-PD1 Antibody as Neoadjuvant Therapy for Microsatellite Stable Locally Advanced Rectal Cancer

NCT05585814 | Recruiting Phase 2

• 1 other identifier: ZHOUHAIYANG
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, single-arm study aims to investigate the efficacy and safety of pembrolizumab plus bevacizumab and chemotherapy as neoadjuvant treatment in pMMR/MSS locally advanced rectal cancer patients

Conditions

Locally Advanced Colorectal Cancer

Outcome Measures

Primary Outcomes (4)

• 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

• Objective response rate

  Percentage of patients who achieve partial response (PR) or complete response (CR)

  3 years

Secondary Outcomes (7)

• Incidence of Treatment-Related Adverse Events

  Until 30 days after the last treatment

• Surgical complications

  Until 90 days after surgery

• Quality of life score (QoL score)

  Until 30 days after the last treatment

• Event free survival

  Up to 3 years

• Disease-free survival

  Up to 3 years

Study Arms (1)

Pembrolizumab+ Bevacizumab + CapeOx as neoadjuvant treatment for 4 cycles

EXPERIMENTAL

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; Pembrolizumab：Pembrolizumab is given intravenously at 200 mg on day 1 every 3 weeks for 4 cycles

Drug: Capecitabine; Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Pembrolizumab

Interventions

Capecitabine DRUG

Capecitabine is given orally at 1000mg / m² twice a day from day1-14 every 3 weeks for 3 cycles

Pembrolizumab+ Bevacizumab + CapeOx as neoadjuvant treatment for 4 cycles

Oxaliplatin DRUG

Oxaliplatin is given by intravenous infusion at 130mg / m2 on Day 1 every 3 weeks for 3cycles

Pembrolizumab+ Bevacizumab + CapeOx as neoadjuvant treatment for 4 cycles

Bevacizumab DRUG

Bevacizumab is given intravenously at 7.5mg/kg on day 1 every 3 weeks for 3 cycles

Pembrolizumab+ Bevacizumab + CapeOx as neoadjuvant treatment for 4 cycles

Pembrolizumab DRUG

Pembrolizumab is given intravenously at 200 mg on day 1 every 3 weeks for 3 cycles

Pembrolizumab+ Bevacizumab + CapeOx as neoadjuvant treatment for 4 cycles

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed rectal adenocarcinoma with cT3+N+M0
• Immunohistochemistry and/or genetic testing confirmed pMMR/MSS
• Initial diagnosed or recurrent patients will be accepted, patients with recurrence should not have received any treatment include chemotherapy, targeted therapy or immunotherapy within 1 month or radiotherapy within 1 year
• Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and haven't received any local treatment.
• 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

You may not qualify if:

• Previously received anti-PD1 or anti-PDL1 or anti-PDL2 or anti-CTLA4.
• Uncontrolled active bleeding from the primary tumor or intestinal obstruction.
• Contraindications of bevacizumab
• 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.

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead

Study Sites (1)

Shanghai Changzheng Hospital

Shanghai, China

RECRUITING

MeSH Terms

Interventions

Capecitabine; Oxaliplatin; Bevacizumab; pembrolizumab

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Haiyang Zhou, MD

CONTACT

+86 81885615; haiyang1985_1@aliyun.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2022
• First Posted: October 19, 2022
• Study Start: May 1, 2023
• Primary Completion: October 1, 2024
• Study Completion (Estimated): May 1, 2028
• Last Updated: March 14, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)