Treatment of Colorectal Liver Metastases With Immunotherapy and Bevacizumab

NCT03698461 | Completed Phase 2

• 1 other identifier: ASA-1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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 term disease-free survival over 3 years is rare and \<20%. More effective measures to prevent recurrence are needed before or after resection of colorectal liver metastases.

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Colonic Neoplasms; Rectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Serial changes in Cluster of Differentiation(CD) 8+ T cell densities

  Opal(TM) platform Immunohistochemistry(IHC)

  Baseline, Day15 of first atezolizumab administration, and after at least 6 cycles (each cycle is 14days)

Secondary Outcomes (9)

• 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)

• Serial changes of Immune cell CD3+, CD8+ densities

  Baseline, Day15 of atezolizumab, and after at least 6 cycles (each cycle is 14days)

• Serial changes of Density of Vascular marker CD31, CD34

  Baseline, Day15 of atezolizumab, and after at least 6 cycles (each cycle is 14days)

• Serial changes of Gene expression profile

  Baseline, Day15 of atezolizumab, and after at least 6 cycles (each cycle is 14days)

• 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

Study Arms (1)

Atezolizumab, Bevacizumab, FOLFOX

EXPERIMENTAL

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)

Drug: Atezolizumab; Drug: Bevacizumab; Drug: Oxaliplatin; Drug: Levoleucovorin; Drug: 5-FU

Interventions

Atezolizumab DRUG

* 1200mg IV on day1 before start of cycle 'atezolizuamb, bevacizumab + FOLFOX(Oxaliplatin, Levoleucovorin, 5-FU') * 840mg IV D1 of C1-12 (Cycle: every 2 weeks)

Also known as: Tecentriq

Atezolizumab, Bevacizumab, FOLFOX

Bevacizumab DRUG

5mg/kg IV D1 of C1-12 (Cycle: every 2 weeks) at least 5 minutes after completion of atezolizumab

Also known as: Avastin

Atezolizumab, Bevacizumab, FOLFOX

Oxaliplatin DRUG

85mg/m2 IV D1 of C1-12 (Cycle: every 2 weeks)

Atezolizumab, Bevacizumab, FOLFOX

Levoleucovorin DRUG

200mg/m2 IV D1 of C1-12 (Cycle: every 2 weeks)

Atezolizumab, Bevacizumab, FOLFOX

5-FU DRUG

* 5-FU Bolus: 400mg/m2 IV bolus D1 of C1-12 (Cycle: every 2 weeks) * 5-FU infusion: 2400mg/mg continuous IV infusion over 46hours D1-3 of C1-12 (Cycle: every 2 weeks)

Also known as: 5-fluorouracil

Atezolizumab, Bevacizumab, FOLFOX

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient-related consideration
• Have provided written informed consent prior to any study specific procedures
• Willing and able to comply with the protocol
• ≧ 20 years of age at the time of signing Informed Consent Form
• Eastern Cooperative Oncology Group (ECOG) status of ≤1
• Disease-related consideration
• Histologically diagnosed colorectal adenocarcinoma
• Liver metastases from colorectal adenocarcinoma confirmed through biopsy
• Liver metastatic lesions should be considered to be potentially resectable after conversion chemotherapy by multi-disciplinary team and should meet one of the following criteria:
• Number of metastatic deposit ≧ 4
• Possibility of resection margin could be involved
• Involvement of major hepatic vessels
• Presence of extrahepatic metastases (if they are supposed to be treated with curative aim and not to alter a plan for hepatic metastasectomy)
• High likelihood of insufficient residual hepatic volume after surgery
• Measurable by RECIST criteria 1.1.

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Extrahepatic metastases that are not candidates for treatment of curative aim (e.g. resection, radiation or radiofrequency ablation)
• Presence of central nervous system (CNS) metastases
• Concurrent or previous history of another primary cancer within 3 years prior to study treatment except for curatively treated cervical cancer in situ, non-melanomatous skin cancer, superficial bladder cancer (pTis or pT1) and curatively treated thyroid cancer of any stage. Concurrent, histologically confirmed, unresected thyroid cancer without distant metastasis could be allowed with the agreement of the principal investigator.
• Chronic alcoholic hepatitis or cirrhosis
• Chronic hepatitis B, defined as HBV DNA (\> 2,000 IU / mL) and ALT\> upper limit of normal range, must be treated with antiviral drugs before enrollment to reach appropriate viral suppression (HBV DNA \<2000 IU / mL), and the antiviral drugs must be maintained during the study treatment period and for 6 months after the last dose of study treatment.
• Prior chemotherapy for metastatic disease
• Uncontrolled medical illness congestive heart failure, myocardial infarction within 6 months including medically uncontrolled infection, uncontrolled hypertension, unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months
• Prior adjuvant FOLFOX chemotherapy
• Prior adjuvant chemotherapy, if administered within 6 months before study entry
• Current or recent (within 10 days of start of study treatment) use of aspirin (\>325mg/day), clopidogrel (\>75mg/day), therapeutic or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (therapeutic anticoagulation on a stable dose for at least 2 weeks prior to the start of study treatment is allowed)
• Known alcohol or drug abuse
• Active infection requiring intravenous antibiotics at the start of study treatment
• Inadequately controlled hypertension (defined as systolic blood pressure \>150mmHg and/or diastolic blood pressure \>100mmHg)
• Prior history of hypertensive crisis or hypertensive encephalopathy

Sponsors & Collaborators

• Asan Medical Center: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Asan Medical Center

Seoul, Songpa-gu, 05505, South Korea

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Colonic Neoplasms; Rectal Neoplasms

Interventions

atezolizumab; Bevacizumab; Oxaliplatin; Levoleucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Leucovorin; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• SunYoung Kim, Ph.D

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 2, 2018
• First Posted: October 9, 2018
• Study Start: May 15, 2019
• Primary Completion: December 22, 2021
• Study Completion: October 24, 2023
• Last Updated: January 31, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)