PD-1 Antibody Plus Bevacizumab and CAPOX as First-line Treatment for RAS-mut MSS mCRC

Colorectal Cancer Clinical Trial

Official title:

PD-1 Antibody Plus Bevacizumab and CAPOX as First-line Treatment for Patients With RAS-mutant, Microsatellite Stable, Metastatic Colorectal Cancer: a Prospective, Open-label, Single-arm, Phase II Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06206096
• Other study ID #: ZLNK-CRC-01
• Status: Recruiting
• Phase: Phase 2
• Start date: May 26, 2021
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: Chinese PLA General Hospital
• Contact: Ru Jia, MD
• Phone: +8613811721720
• Email: ashleyjr[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to explore the efficacy and safety of anti-PD-1 antibody plus bevacizumab and chemotherapy as first-line treatment for patients with RAS-mutant, microsatellite stable, metastatic colorectal cancer.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed non resectable, locally advanced or metastatic colorectal cancer;

• No previous anti-tumor treatment for metastatic diseases;

• KRAS/NRAS mutation;

• Eastern Cooperation Oncology Group (ECOG) performance status of 0-1;

• Life expectancy = 3 months;

• Adequate organ and bone marrow functions:

Absolute neutrophil count=1.5x10^9/L; Platelet count=100x10^9/L; Hemoglobin=9g/dL; Serum bilirubin<1.5x the upper limit of normal(ULN); Alanine aminotransferase(ALT) and aspartate aminotransferase(AST)<1.5x ULN; Serum creatinine<1.5x ULN; Endogenous creatinine clearance rate = 50ml / min;

• Women of childbearing age need to take effective contraceptive measures.

Exclusion Criteria:

• Previous treatment with vascular endothelial growth factor receptor (VEGFR) inhibitors or previous use of immune checkpoint inhibitors;

• With BRAF mutation or MSI-H status;

• Other untreated or concurrent tumors (except cervical carcinoma in situ, treated basal cell carcinoma or superficial bladder tumor, or if the tumor is cured and there is no evidence of disease for more than 3 years);

• Have received other systemic anti-tumor treatments, including chemotherapy, signal transduction inhibitors, hormone therapy and immunotherapy within 4 weeks before enrollment;

• There was central nervous system (CNS) metastasis or previous brain metastasis before enrollment;

• Have received any surgery or invasive treatment or operation within 4 weeks before enrollment;

• Have received Local anti-tumor therapy such as hepatic artery interventional embolization, liver metastasis cryoablation or radiofrequency ablation within 4 weeks before enrollment;

• Uncontrolled malignant ascites;

• Participated in other clinical trials within 4 weeks before enrollment, and received corresponding experimental drug treatment;

• Allergic to the study drug or any of its adjuvants;

• International normalized ratio (INR) > 1.5 or partially activated prothrombin time (APTT) > 1.5 × ULN;

• The researchers judged clinically significant electrolyte abnormalities;

• Hypertension that cannot be controlled by drugs, which is specified as: systolic blood pressure = 140 mmHg and / or diastolic blood pressure = 90 mmHg; Patients currently have poorly controlled diabetes (fasting glucose level is greater than CTCAE grade 2 after regular treatment);

• Patients with dysphagia, active peptic ulcer, intestinal obstruction, active gastrointestinal bleeding, peptic perforation, malabsorption syndrome or uncontrolled intestinal inflammatory diseases;

• Any disease or state affecting drug absorption before enrollment, or the patient cannot take oral medication;

• Patients with obvious evidence of bleeding tendency or medical history within 3 months before enrollment, hemoptysis or thromboembolism within 12 months;

• Cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe / unstable angina pectoris or coronary artery bypass grafting within 6 months before enrollment; Congestive heart failure, New York Heart Association (NYHA) grade > 2; ventricular arrhythmia requiring drug treatment; LVEF (left ventricular ejection fraction) < 50%;

• Active infection or serious infection that is not controlled by drug (=CTCAE v5.0 Grade 2);

• History of clinically significant hepatic disease, including, but not limited to, known hepatitis B virus (HBV) infection with HBV DNA positive (copies =1×10^4/ml or >2000 IU/ml); known hepatitis C virus infection with HCV RNA positive (copies =1×10^3/m); hepatitis and cirrhosis;

• Women who are pregnant or lactating;

• Urinary protein = ++, and the 24-hour urine protein quantification is greater than 1.0g;

• Have any other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other conditions that makes the subject not suitable for enrolling according to the judgment of the investigator.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Microsatellite Stable Colorectal Carcinoma
• RAS Mutation

Intervention

Drug:
• oxaliplatin+capecitabine+bevacizumab+PD-1 antibody
oxaliplatin will be administered once every 3 weeks at a dose of 130 mg/m2; Capecitabine will be taken orally at a dose of 1g/m2 twice daily for continuous oral administration over 14 days; Bevacizumab will be administered intravenously every 3 weeks at a dose of 7.5 mg/kg; PD-1 antibody was given due to different types.

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR	The proportion of patients with a confirmed complete response or partial response	up to 3 years
Secondary	PFS	The time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first	up to 3 years
Secondary	OS	The time from randomization to death from any reason	up to 3 years
Secondary	DCR	The proportion of patients with a best overall response of confirmed complete or partial response, or stable disease (CR+ PR + SD)	up to 3 years
Secondary	Safety and tolerability by incidence, severity and outcome of adverse events	Safety and tolerance will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 5.0	up to 3 years