Treatment of Colorectal Liver Metastases With Immunotherapy and Bevacizumab

Phase 2

Completed

• Conditions: Colorectal Neoplasms; Neoplasm Metastasis; Colonic Neoplasms; Rectal Neoplasms
• Interventions: Drug: Atezolizumab; Drug: Bevacizumab; Drug: Oxaliplatin; Drug: Levoleucovorin; Drug: 5-FU

• Registration Number: NCT03698461
• Lead Sponsor: Asan Medical Center

Brief Summary

Liver is the most common site of metastases from colorectal cancer. Neoadjuvant chemotherapy with targeted agents is usually recommended for borderline-resectable liver metastases that are technically difficult to resect for conversion to resectable disease and control of metastatic spread. However, the prognosis of these patients are still poor, and long te...

Detailed Description

* Atezolizumab is a humanized immunoglobulin G1 monoclonal antibody that targets Programmed Death-Ligand 1(PD-L1) and inhibits the interaction between PD-L1 and its receptors, Programmed cell Death protein 1(PD-1) and B7.1. Therapeutic blockade of PD-L1 binding by atezolizumab has been shown to enhance the magnitude and quality of tumor specific T cell respo...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-10-02
• Study First Submitted QC: 2018-10-04
• Study First Posted: 2018-10-09
• Study Start: 2019-05-15
• Primary Completion: 2021-12-22
• Study Completion: 2023-10-24
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-29
• Last Update Posted: 2024-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Atezolizumab, Bevacizumab, FOLFOX	Atezolizumab	Atezolizumab 1200mg IV Once, Atezolizumab (840mg IV D1 of C1-12) + Bevacizumab (5mg/kg IV D1 of C1-12) + FOLFOX(Oxaliplatin 85mg/m2 IV D1 of C1-12, Levoleucovorin 200mg/m2 IV D1 of C1-12, 5-FU - bolus 400mg/m2 IV D1 of C1-12, - infusional 2400mg/m2 IV continuous(46 hours) D1-3 of C1-12)
Atezolizumab, Bevacizumab, FOLFOX	Bevacizumab	Atezolizumab 1200mg IV Once, Atezolizumab (840mg IV D1 of C1-12) + Bevacizumab (5mg/kg IV D1 of C1-12) + FOLFOX(Oxaliplatin 85mg/m2 IV D1 of C1-12, Levoleucovorin 200mg/m2 IV D1 of C1-12, 5-FU - bolus 400mg/m2 IV D1 of C1-12, - infusional 2400mg/m2 IV continuous(46 hours) D1-3 of C1-12)
Atezolizumab, Bevacizumab, FOLFOX	Oxaliplatin	Atezolizumab 1200mg IV Once, Atezolizumab (840mg IV D1 of C1-12) + Bevacizumab (5mg/kg IV D1 of C1-12) + FOLFOX(Oxaliplatin 85mg/m2 IV D1 of C1-12, Levoleucovorin 200mg/m2 IV D1 of C1-12, 5-FU - bolus 400mg/m2 IV D1 of C1-12, - infusional 2400mg/m2 IV continuous(46 hours) D1-3 of C1-12)
Atezolizumab, Bevacizumab, FOLFOX	Levoleucovorin	Atezolizumab 1200mg IV Once, Atezolizumab (840mg IV D1 of C1-12) + Bevacizumab (5mg/kg IV D1 of C1-12) + FOLFOX(Oxaliplatin 85mg/m2 IV D1 of C1-12, Levoleucovorin 200mg/m2 IV D1 of C1-12, 5-FU - bolus 400mg/m2 IV D1 of C1-12, - infusional 2400mg/m2 IV continuous(46 hours) D1-3 of C1-12)
Atezolizumab, Bevacizumab, FOLFOX	5-FU	Atezolizumab 1200mg IV Once, Atezolizumab (840mg IV D1 of C1-12) + Bevacizumab (5mg/kg IV D1 of C1-12) + FOLFOX(Oxaliplatin 85mg/m2 IV D1 of C1-12, Levoleucovorin 200mg/m2 IV D1 of C1-12, 5-FU - bolus 400mg/m2 IV D1 of C1-12, - infusional 2400mg/m2 IV continuous(46 hours) D1-3 of C1-12)

Primary Outcome Measures

Name	Time	Method
Serial changes in Cluster of Differentiation(CD) 8+ T cell densities	Baseline, Day15 of first atezolizumab administration, and after at least 6 cycles (each cycle is 14days)	Opal(TM) platform Immunohistochemistry(IHC)

Secondary Outcome Measures

Name	Time	Method
Serial changes of Density of Vascular marker CD31, CD34	Baseline, Day15 of atezolizumab, and after at least 6 cycles (each cycle is 14days)	Opal(TM) platform IHC
Serial changes of Gene expression profile	Baseline, Day15 of atezolizumab, and after at least 6 cycles (each cycle is 14days)	RNA-seq
Response Rate	Baseline, at 6th week from the first treatment, and then every 6±2 weeks up to 12 cycles (each cycle is 14days), every 3 months after the 12 cycles up to 24months	RECIST 1.1 and immune RECIST(iRECIST)
Serial changes of Immune cell biomarkers CD3, CD4, Programmed death-Ligand 1(PD-L1),PD-1, granzyme B, CD45RO, Forkhead Box P3(FOXP3), CD68	Baseline, Day15 of atezolizumab, and after at least 6 cycles (each cycle is 14days)	Opal(TM) platform IHC
Serial changes of Immune cell CD3+, CD8+ densities	Baseline, Day15 of atezolizumab, and after at least 6 cycles (each cycle is 14days)	IMMUNOSCORE® (IMMUNOSCORE is a registered trademark owned by INSERM)
Incidence, nature and severity of adverse events with severity (Safety profile)	Consent to 90 days after the last dose of investigational medicinal product or until initiation of new systemic anti-cancer therapy, whichever occurs first.	Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Microbiome profile	Day1 before first atezolizumab administration, Day15 before the treatment and at time of hepatic metastasectomy or liver biopsy after 6 cycles of treatment (each cycle is 14days)	In stool samples through whole metagenomic sequencing
R0 resection rate	At the time of hepatic resection	All gross lesions are resected and all surgical margins are free from tumor cells (The proportion of patients who undergo R0 resection for liver metastases out of all patients who started at least one dose of study treatment.)
Progression-Free Survival	Baseline, at 6th week from the first treatment, and then every 6±2 weeks up to 12 cycles (each cycle is 14days), every 3 months after the 12 cycles up to 24months	RECIST 1.1 and iRECIST

Trial Locations

Locations (1)

Asan Medical Center; 🇰🇷 Seoul, Songpa-gu, Korea, Republic of