Preoperative Pembrolizumab Plus Bevacizumab Combined With Chemotherapy in Patients With pMMR/MSS Locally Advanced Colorectal Cancer (COBP)

Safety and Efficacy of Pembrolizumab Combined With CAPOX Plus Bevacizumab as Neoadjuvant Treatment of pMMR/MSS Locally Advanced Colorectal Cancer Patients：a Single-arm, Phase II, Prospective Study

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

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced Colorectal Cancer
• Intervention / Treatment: Drug: Capecitabine; Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 2

Contacts and Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed colorectal adenocarcinoma with T4bNxM0 and radical operation cannot be achieved by investigator's evaluation
• 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

Exclusion Criteria:

• 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.
• 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: Pembrolizumab+ Bevacizumab + CAPOX as neoadjuvant treatment for 4 cycles; CapOx: Capecitabine is given orally at 1500mg / m² twice a day from day1-14 every 3 weeks for 4 cycles and Oxaliplatin is given by intravenous infusion at 200mg / m2 on Day 1 every 3 weeks for 4 cycles; Bevacizumab：Bevacizumab is given intravenously at 10mg/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; Capecitabine is given orally at 1500mg / m² twice a day from day1-14 every 3weeks for 3 cycles; Drug: Oxaliplatin; Oxaliplatin is given by intravenous infusion at 200mg / m2 on Day 1 every 3 weeks for 3cycles; Drug: Bevacizumab; Bevacizumab is given intravenously at 10mg/kg on day 1 every 3 weeks for 3 cycles; Drug: Pembrolizumab; Pembrolizumab is given intravenously at 200 mg on day 1 every 3 weeks for 3 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST)	3 years
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
Incidence of Treatment-Related Adverse Events	Number of adverse events	Until 30 days after the last treatment
Quality of life score (QoL score)	Assessment of life quality based on EORTC QLQ-C30	Until 30 days after the last treatment

Collaborators and Investigators

• Sponsor: Shanghai Changzheng Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): October 1, 2025

Study Registration Dates

• First Submitted: October 9, 2022
• First Submitted That Met QC Criteria: October 18, 2022
• First Posted (Actual): October 19, 2022

Study Record Updates

• Last Update Posted (Actual): October 19, 2022
• Last Update Submitted That Met QC Criteria: October 18, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

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

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