Clinical trial NCT03289533: A Study Of Avelumab In Combination With Axitinib In Advanced HCC (VEGF Liver 100)
Official title: AN OPEN LABEL, SINGLE ARM PHASE 1B STUDY OF AVELUMAB PLUS AXITINIB AS FIRST LINE TREATMENT IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Hepatocellular
Keywords: Cancer
Hepatocellular carcinoma
Liver disease
Avelumab
Axitinib
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-09-21
Enrollment: 22
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the safety, efficacy and PK of avelumab in combination with axitinib as first line treatment in patients with advanced HCC


Eligibility criteria: Inclusion Criteria:

* Diagnosis of locally advanced or metastatic HCC, obtained by histology/cytology (on a prior tumor biopsy) or by imaging with serum α-fetoprotein (AFP) ≥400 ng/mL.
* All patients must provide at least 1 archival tumor specimen. If archival tumor specimen is no longer available, de novo tumor biopsy will be required during screening.
* HCC not amenable to local therapy.
* Measurable disease according to RECIST v. 1.1.
* Child Pugh Class A disease.
* BCLC stage B or C disease.
* No evidence of uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart.
* ECOG performance status 0 or 1.
* Adequate bone marrow function, renal and liver functions
* Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (LLN) as assessed by multigated acquisition (MUGA) scan or echocardiogram (ECHO).

Exclusion Criteria:

* Prior systemic treatment for advanced HCC, including prior treatment with approved or investigational drugs.
* Any prior locoregional therapy within 4 weeks and radiotherapy or surgical procedure within 2 weeks (4 weeks for major surgery) of enrollment.
* Patients with known symptomatic brain metastases requiring steroids.
* Presence of hepatic encephalopathy (ie, Child Pugh score of 2 or 3) and/or clinically relevant ascites (ie, Child Pugh score of 3).
* Presence of main portal vein invasion by HCC.
* Any of the following within the 12 months prior to enrollment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, LVEF less than LLN, clinically significant pericardial effusion, cerebrovascular accident, transient ischemic attack.
* Active infection requiring systemic therapy except for hepatitis C virus (HCV) and hepatitis B virus (HBV).

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.03
timeFrame: From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)
measure: Number of Participants With Abnormal Laboratory Parameter Values (Hematology) as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version 4.03
timeFrame: From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)
measure: Number of Participants With Abnormal Laboratory Parameter Values (Chemistry) as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version (v) 4.03
timeFrame: From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)
Secondary outcomes:
measure: Time to Disease Progression (TTP)
timeFrame: From first dose of study drug until first documentation of progressive disease or data censoring date, whichever occurred first (maximum up to 20 months)
measure: Progression Free Survival (PFS)
timeFrame: From first dose of study drug until first documentation of PD or death due to any cause or data censoring date, whichever occurred first (maximum up to 20 months)
measure: Percentage of Participants With Objective Response (OR)
timeFrame: From first dose of study drug until disease progression or death due to any cause (maximum up to 20 months)
measure: Percentage of Participants With Disease Control (DC)
timeFrame: From first dose of study drug until first documentation of CR or PR or SD or till non-CR/non-PD (maximum up to 20 months)
measure: Time to Tumor Response (TTR)
timeFrame: From first dose of study drug until first documentation of CR or PR (maximum up to 20 months)
measure: Duration of Response (DR)
timeFrame: From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (maximum up to 20 months)
measure: Overall Survival (OS)
timeFrame: From first dose of study drug to date of death from any cause or data censoring date, whichever occurred first (maximum up to 21 months)
measure: Maximum Observed Serum Concentration of Avelumab
timeFrame: Pre-dose, at the end of avelumab infusion on Day 1 of Cycle 2, 3, 4 (Duration of each cycle=14 days)
measure: Maximum Observed Plasma Concentration of Axitinib
timeFrame: Pre-dose, 2 hours post dose Axitinib administration on Day 1 of Cycle 2, 3 (Duration of each cycle=14 days)
measure: Pre-dose Serum Concentration of Avelumab
timeFrame: Pre-dose on Day 1 of Cycle 2, 3, 4, 6, 8, 12, 16, 20, 24, 28 (Duration of each cycle=14 days)
measure: Pre-dose Plasma Concentration of Axitinib
timeFrame: Pre-dose on Day 1 of Cycle 2 and 3 (Duration of each cycle=14 days)
measure: Number of Participants With Their Target Programmed Death-Ligand 1 (PD-L1) Status
timeFrame: Baseline (Day 1)
measure: Mean Percentage of CD8+ Cells in Per Unit Area of Invasive Margin, Center of Tumor Cells and Total Area of Tumor Cells
timeFrame: From first dose of study drug up to end of treatment (maximum up to 20 months)
measure: Summary of Cluster of Differentiation 8 (CD8+) Cells Expression: Total Area Covered by CD8+ Cells in Center of Tumor Cells
timeFrame: From first dose of study drug up to end of treatment (up to 20 months)
measure: Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Positive Neutralizing Antibodies (nAbs)
timeFrame: From first dose of study drug until 30 days after the last dose of study drug (maximum up to 21 months)
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: Iizuka
country: Japan
facility: Iizuka Hospital
state: Fukuoka
city: Osaka-Sayama
country: Japan
facility: Kindai University Hospital, Department of Gastroenterology and Hepatology
state: Osaka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Mitaka-shi
country: Japan
facility: Kyorin University Hospital, Department of Medical Oncology
state: Tokyo
city: Musashino
country: Japan
facility: Japanese Red Cross Musashino Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Medical Center
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: