The Efficacy and Safety of Toripalimab Combined With Bevacizumab and Chemotherapy as Neoadjuvant Therapy in Patients With Advanced MSI-H or dMMR Colorectal Cancer: an Open-label, Multicenter, Single-arm, Phase Ib/II Study

Peking University1 site in 1 country44 target enrollmentDecember 24, 2020

ConditionsColorectal Carcinoma

InterventionsToripalimab Bevacizumab Irinotecan

DrugsToripalimab Bevacizumab Irinotecan

Overview

Phase: Phase 1
Intervention: Toripalimab
Conditions: Colorectal Carcinoma
Sponsor: Peking University
Enrollment: 44
Locations: 1
Primary Endpoint: Pathological complete response rate based on blinded, independent, central review
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a trial investigating the efficacy and safety of Toripalimab combined with bevacizumab and chemotherapy as neoadjuvant therapy in patients with advanced microsatellite instability-high (MSI-H) or DNA mismatch repair-deficient (dMMR) colorectal cancer.

Registry

clinicaltrials.gov

Start Date

December 24, 2020

End Date

December 24, 2023

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Peking University

Responsible Party

Principal Investigator

Shen Lin

Professor

Peking University

Eligibility Criteria

Inclusion Criteria

•Histologically confirmed colorectal adenocarcinoma meeting any of the following criterion: a) T3-4 resectable rectal cancer; b) T1-2 rectal cancer located within 12 cm from the anal verge and refusing direct surgery or radiation therapy; c) T4a-b resectable colon cancer.
•Microsatellite instability-high (MSI-H) or DNA mismatch repair-deficient (dMMR).
•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-
•Fully aware of this study and having signed informed consent.
•Age 18 to 75 years old without gender limitation.
•Good compliance.
•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.

Exclusion Criteria

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

Arms & Interventions

Toripalimab combined with bevacizumab and chemotherapy

Intervention: Toripalimab

Toripalimab combined with bevacizumab and chemotherapy

Intervention: Bevacizumab

Toripalimab combined with bevacizumab and chemotherapy

Intervention: Irinotecan

Outcomes

Primary Outcomes

Pathological complete response rate based on blinded, independent, central review

Time Frame: 10 weeks

Percentage of patients who achieve pathological complete response (pCR) based on blinded, independent, central review (BICR).

Secondary Outcomes

R0 recession rate(10 weeks)
Time to surgery(10 weeks)
Pathological complete response rate assessed by local investigator(10 weeks)
Objective response rate(Up to 3 years)
Score of life quality(Until 30 days after the last treatment)
Pathological complete response rate based on blinded, independent, central review (BICR) and the assessment of local investigator(10 weeks)
Tumor regression grade (TRG)(10 weeks)
Event free survival(Up to 3 years)
Disease-free survival(Up to 3 years)
One-year or two-year disease-free survival rate(Up to 2 years)
One-year or two-year overall survival rate(Up to 2 years)
Incidence of Treatment-Related Adverse Events(Until 30 days after the last treatment)