Back to resultsA Study Of Avelumab In Combination With Axitinib In Advanced HCC (VEGF Liver 100)
Primary Purpose
Carcinoma, Hepatocellular
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Avelumab (MSB0010718C)
Axitinib (AG-013736)
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Hepatocellular focused on measuring Cancer, Hepatocellular carcinoma, Liver disease, Avelumab, Axitinib
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).
Sites / Locations
- Aichi Cancer Center Hospital
- Iizuka Hospital
- Kindai University Hospital, Department of Gastroenterology and Hepatology
- National Cancer Center Hospital
- Kyorin University Hospital, Department of Medical Oncology
- Japanese Red Cross Musashino Hospital
- National Hospital Organization Kyushu Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Experimental 1
Arm Description
Avelumab (MSB0010718C) in combination with axitinib (AG-013736)
Outcomes
Primary Outcome Measures
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
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were graded by investigator according to NCI CTCAE v.4.03 as follows: Grade 1: mild AE, Grade 2: moderate AE, Grade 3: severe AE, Grade 4: life-threatening consequences and urgent intervention indicated, Grade 5: death related to AE.
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
As per NCI-CTCAE v 4.03, anemia Grade 1= Less than (<) lower limit of normal (LLN) to 100 gram per liter (g/L),Grade 2= <100 to 80 g/L; hemoglobin increased: Grade 1= increase of greater than (>) 0 to 2 gram per deciliter(g/dL) above upper limit of normal [ULN]; lymphocyte count decreased: Grade 1= <LLN to 0.8*10^9/L, Grade 2= <0.8*10^9/L to 0.5*10^9/L, Grade 3= <0.5*10^9/L to 0.2*10^9/L ; lymphocyte count increased: Grade 2= >4*10^9/L to 20*10^9/L; neutrophil count decreased: Grade 1= <LLN to 1.5*10^9/L ,Grade 2= <1.5*10^9/L to 1.0*10^9/L; platelet count decreased: Grade 1= <LLN to 75.0*10^9/L, Grade 2= <75.0*10^9/L to 50.0*10^9/L; white blood cell decreased: Grade 1= <LLN to 3*10^9/L, Grade 2= <3*10^9/L to 2*10^9/L.
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
ALT,ALP,AST increased grades(g):g1>ULN-3.0*ULN,g2>3.0-5.0*ULN,g3>5.0-20.0*ULN; blood bilirubin increased:g1>ULN-1.5*ULN, g2>1.5-3.0*ULN, g3>3.0-10.0*ULN; [cholesterol high:g1>ULN-7.75, g2 >7.75-10.34,g4 >12.92]millimoles per liter(mmol/L);creatine phosphokinase, gamma-glutamyl transferase(ggt) increased g1>ULN-2.5*ULN, g2>2.5*ULN-5*ULN; Ggt increased g3 >5.0-20.0*ULN; Creatinine increased: g1>ULN-1.5*ULN; [hypoalbuminemia:g1<LLN-30,g2<30-20] grams per liter(g/L);[hyperglycemia:g1> ULN-8.9,g2> 8.9-13.9,g3> 13.9-27.8;hypermagnesemia:g1>ULN-1.23;hypercalcemia:g1>ULN -2.9;hyperkalemia:g1>ULN-5.5,hypernatremia:g1>ULN-150;hypertriglyceridemia g1:1.71-3.42,g2 >3.42-5.7;hypocalcemia:g1<LLN-2.0,hypoglycemia:g1<LLN-3.0, g2<3.0-2.2;hypokalemia:g2<LLN-3.0,g4<2.5,hypomagnesemia:g1<LLN-0.5,hyponatremia:g1<LLN-130, g3<130-120,hypophosphatemia:g1<LLN-0.8,g2<0.8-0.6]mmol/L;lipase increased:g1>ULN-1.5*ULN,g3 >2.0-5.0*ULN;serum amylase increased:g1>ULN-1.5*ULN, g2>1.5-2.0*ULN,g3>2.0-5.0*ULN.
Secondary Outcome Measures
Time to Disease Progression (TTP)
TTP as assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, was define as time (in months) from date of first dose of study drug to date of first documentation of progressive disease (PD) or data censoring date, whichever occurred first. PD was defined as greater than or equal to (>=) 20 percent (%) increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment), with a minimum absolute increase of at least 5 millimeter (mm), or appearance of >=1 new lesions. TTP was analyzed by Kaplan-Meier method. TTP data was censored on the date the last adequate tumor assessment for participants without PD, for participants who start new anti-cancer treatment prior to PD, for participants who died without PD, or for participants with PD after >=2 missing tumor assessments.
Progression Free Survival (PFS)
PFS as assessed by investigator per RECIST v1.1, was defined as time (in months) from date of first dose of study drug to date of first documentation of PD or death due to any cause or data censoring date, whichever occurred first. PD: >= 20% increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment). The sum must also demonstrate absolute increase of >=5 mm, or appearance of >=1 new lesions. PFS was analyzed by Kaplan-Meier method. PFS data was censored on the date the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to PFS event, for participants with a PFS event after >=2 missing tumor assessments.
Percentage of Participants With Objective Response (OR)
OR as assessed by investigator per RECIST v.1.1, was defined as participants with confirmed best overall response of complete response (CR) or partial response (PR), were recorded from first dose of study drug until disease progression or death due to any cause. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm. PR was defined as >=30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.
Percentage of Participants With Disease Control (DC)
Disease control as assessed by investigator according to RECIST v1.1, was defined as participants with CR, PR, stable disease (SD), or non-CR/non-PD. CR: disappearance of all target and non-target lesions and sustained for 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: >= 30% decrease in sum of diameters of target lesions taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm or appearance of >=1 new lesions. Non-CR/non-PD: Persistence of any non-target lesions and/or tumor marker level above the normal limit at >=8 weeks after date of first dose of study treatment.
Time to Tumor Response (TTR)
TTR as assessed by investigator according to RECIST v1.1 was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) that was subsequently confirmed. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: >= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters.
Duration of Response (DR)
DR as assessed by investigator according to RECIST v1.1, was defined as the time from date of first documentation of objective response (CR or PR) to date of PD or death due to any cause, or data censoring date, whichever occurred first. CR: disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) reduced in short axis to <10 mm. PR: >= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study treatment, with absolute increase of at least 5 mm or appearance of >=1 new lesions. DR data was censored on the date of last adequate tumor assessment for participants without an event (CR, PR, PD or death), for participants who start new anti-cancer treatment prior to DR assessment, for participants with DR assessment after >=2 missing tumor assessments.
Overall Survival (OS)
OS was defined as the time (in months) from the date of first dose of study drug to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at the date of last contact. OS was analyzed by Kaplan-Meier method.
Maximum Observed Serum Concentration of Avelumab
Maximum Observed Plasma Concentration of Axitinib
Pre-dose Serum Concentration of Avelumab
Pre-dose Plasma Concentration of Axitinib
Number of Participants With Their Target Programmed Death-Ligand 1 (PD-L1) Status
PD-L1 status was defined as positive when PD-L1 staining of any intensity was observed in tumor-associated immune cells covering >= 1% of the tumor area. PD-L1 status was defined as negative when PD-L1 staining of any intensity was observed in tumor-associated immune cells covering < 1% of the tumor area.
Mean Percentage of CD8+ Cells in Per Unit Area of Invasive Margin, Center of Tumor Cells and Total Area of Tumor Cells
CD8+ cells are the type of T-lymphocytes. Invasive margin is defined as the region on each side of the border between tumor cells. Expression of CD8+ cells in invasive margin, center of tumor cells, total area of tumor cells has been reported as mean percentage of CD8+cells per unit area. Area was measured in millimeter square (mm^2).
Summary of Cluster of Differentiation 8 (CD8+) Cells Expression: Total Area Covered by CD8+ Cells in Center of Tumor Cells
CD8+ cells are the type of T-lymphocytes.
Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Positive Neutralizing Antibodies (nAbs)
ADA positive was defined as presence of at least one positive ADA sample. nAb positive was defined as presence of at least one positive nAb sample.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03289533
Brief Title
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
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
September 8, 2017 (Actual)
Primary Completion Date
August 27, 2019 (Actual)
Study Completion Date
October 25, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
To evaluate the safety, efficacy and PK of avelumab in combination with axitinib as first line treatment in patients with advanced HCC
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Hepatocellular
Keywords
Cancer, Hepatocellular carcinoma, Liver disease, Avelumab, Axitinib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Experimental 1
Arm Type
Experimental
Arm Description
Avelumab (MSB0010718C) in combination with axitinib (AG-013736)
Intervention Type
Drug
Intervention Name(s)
Avelumab (MSB0010718C)
Intervention Description
Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID.
Intervention Type
Drug
Intervention Name(s)
Axitinib (AG-013736)
Intervention Description
Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID.
Primary Outcome Measure Information:
Title
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
Description
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were graded by investigator according to NCI CTCAE v.4.03 as follows: Grade 1: mild AE, Grade 2: moderate AE, Grade 3: severe AE, Grade 4: life-threatening consequences and urgent intervention indicated, Grade 5: death related to AE.
Time Frame
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)
Title
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
Description
As per NCI-CTCAE v 4.03, anemia Grade 1= Less than (<) lower limit of normal (LLN) to 100 gram per liter (g/L),Grade 2= <100 to 80 g/L; hemoglobin increased: Grade 1= increase of greater than (>) 0 to 2 gram per deciliter(g/dL) above upper limit of normal [ULN]; lymphocyte count decreased: Grade 1= <LLN to 0.8*10^9/L, Grade 2= <0.8*10^9/L to 0.5*10^9/L, Grade 3= <0.5*10^9/L to 0.2*10^9/L ; lymphocyte count increased: Grade 2= >4*10^9/L to 20*10^9/L; neutrophil count decreased: Grade 1= <LLN to 1.5*10^9/L ,Grade 2= <1.5*10^9/L to 1.0*10^9/L; platelet count decreased: Grade 1= <LLN to 75.0*10^9/L, Grade 2= <75.0*10^9/L to 50.0*10^9/L; white blood cell decreased: Grade 1= <LLN to 3*10^9/L, Grade 2= <3*10^9/L to 2*10^9/L.
Time Frame
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)
Title
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
Description
ALT,ALP,AST increased grades(g):g1>ULN-3.0*ULN,g2>3.0-5.0*ULN,g3>5.0-20.0*ULN; blood bilirubin increased:g1>ULN-1.5*ULN, g2>1.5-3.0*ULN, g3>3.0-10.0*ULN; [cholesterol high:g1>ULN-7.75, g2 >7.75-10.34,g4 >12.92]millimoles per liter(mmol/L);creatine phosphokinase, gamma-glutamyl transferase(ggt) increased g1>ULN-2.5*ULN, g2>2.5*ULN-5*ULN; Ggt increased g3 >5.0-20.0*ULN; Creatinine increased: g1>ULN-1.5*ULN; [hypoalbuminemia:g1<LLN-30,g2<30-20] grams per liter(g/L);[hyperglycemia:g1> ULN-8.9,g2> 8.9-13.9,g3> 13.9-27.8;hypermagnesemia:g1>ULN-1.23;hypercalcemia:g1>ULN -2.9;hyperkalemia:g1>ULN-5.5,hypernatremia:g1>ULN-150;hypertriglyceridemia g1:1.71-3.42,g2 >3.42-5.7;hypocalcemia:g1<LLN-2.0,hypoglycemia:g1<LLN-3.0, g2<3.0-2.2;hypokalemia:g2<LLN-3.0,g4<2.5,hypomagnesemia:g1<LLN-0.5,hyponatremia:g1<LLN-130, g3<130-120,hypophosphatemia:g1<LLN-0.8,g2<0.8-0.6]mmol/L;lipase increased:g1>ULN-1.5*ULN,g3 >2.0-5.0*ULN;serum amylase increased:g1>ULN-1.5*ULN, g2>1.5-2.0*ULN,g3>2.0-5.0*ULN.
Time Frame
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 Outcome Measure Information:
Title
Time to Disease Progression (TTP)
Description
TTP as assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, was define as time (in months) from date of first dose of study drug to date of first documentation of progressive disease (PD) or data censoring date, whichever occurred first. PD was defined as greater than or equal to (>=) 20 percent (%) increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment), with a minimum absolute increase of at least 5 millimeter (mm), or appearance of >=1 new lesions. TTP was analyzed by Kaplan-Meier method. TTP data was censored on the date the last adequate tumor assessment for participants without PD, for participants who start new anti-cancer treatment prior to PD, for participants who died without PD, or for participants with PD after >=2 missing tumor assessments.
Time Frame
From first dose of study drug until first documentation of progressive disease or data censoring date, whichever occurred first (maximum up to 20 months)
Title
Progression Free Survival (PFS)
Description
PFS as assessed by investigator per RECIST v1.1, was defined as time (in months) from date of first dose of study drug to date of first documentation of PD or death due to any cause or data censoring date, whichever occurred first. PD: >= 20% increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment). The sum must also demonstrate absolute increase of >=5 mm, or appearance of >=1 new lesions. PFS was analyzed by Kaplan-Meier method. PFS data was censored on the date the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to PFS event, for participants with a PFS event after >=2 missing tumor assessments.
Time Frame
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)
Title
Percentage of Participants With Objective Response (OR)
Description
OR as assessed by investigator per RECIST v.1.1, was defined as participants with confirmed best overall response of complete response (CR) or partial response (PR), were recorded from first dose of study drug until disease progression or death due to any cause. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm. PR was defined as >=30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame
From first dose of study drug until disease progression or death due to any cause (maximum up to 20 months)
Title
Percentage of Participants With Disease Control (DC)
Description
Disease control as assessed by investigator according to RECIST v1.1, was defined as participants with CR, PR, stable disease (SD), or non-CR/non-PD. CR: disappearance of all target and non-target lesions and sustained for 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: >= 30% decrease in sum of diameters of target lesions taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm or appearance of >=1 new lesions. Non-CR/non-PD: Persistence of any non-target lesions and/or tumor marker level above the normal limit at >=8 weeks after date of first dose of study treatment.
Time Frame
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)
Title
Time to Tumor Response (TTR)
Description
TTR as assessed by investigator according to RECIST v1.1 was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) that was subsequently confirmed. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: >= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters.
Time Frame
From first dose of study drug until first documentation of CR or PR (maximum up to 20 months)
Title
Duration of Response (DR)
Description
DR as assessed by investigator according to RECIST v1.1, was defined as the time from date of first documentation of objective response (CR or PR) to date of PD or death due to any cause, or data censoring date, whichever occurred first. CR: disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) reduced in short axis to <10 mm. PR: >= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study treatment, with absolute increase of at least 5 mm or appearance of >=1 new lesions. DR data was censored on the date of last adequate tumor assessment for participants without an event (CR, PR, PD or death), for participants who start new anti-cancer treatment prior to DR assessment, for participants with DR assessment after >=2 missing tumor assessments.
Time Frame
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)
Title
Overall Survival (OS)
Description
OS was defined as the time (in months) from the date of first dose of study drug to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at the date of last contact. OS was analyzed by Kaplan-Meier method.
Time Frame
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)
Title
Maximum Observed Serum Concentration of Avelumab
Time Frame
Pre-dose, at the end of avelumab infusion on Day 1 of Cycle 2, 3, 4 (Duration of each cycle=14 days)
Title
Maximum Observed Plasma Concentration of Axitinib
Time Frame
Pre-dose, 2 hours post dose Axitinib administration on Day 1 of Cycle 2, 3 (Duration of each cycle=14 days)
Title
Pre-dose Serum Concentration of Avelumab
Time Frame
Pre-dose on Day 1 of Cycle 2, 3, 4, 6, 8, 12, 16, 20, 24, 28 (Duration of each cycle=14 days)
Title
Pre-dose Plasma Concentration of Axitinib
Time Frame
Pre-dose on Day 1 of Cycle 2 and 3 (Duration of each cycle=14 days)
Title
Number of Participants With Their Target Programmed Death-Ligand 1 (PD-L1) Status
Description
PD-L1 status was defined as positive when PD-L1 staining of any intensity was observed in tumor-associated immune cells covering >= 1% of the tumor area. PD-L1 status was defined as negative when PD-L1 staining of any intensity was observed in tumor-associated immune cells covering < 1% of the tumor area.
Time Frame
Baseline (Day 1)
Title
Mean Percentage of CD8+ Cells in Per Unit Area of Invasive Margin, Center of Tumor Cells and Total Area of Tumor Cells
Description
CD8+ cells are the type of T-lymphocytes. Invasive margin is defined as the region on each side of the border between tumor cells. Expression of CD8+ cells in invasive margin, center of tumor cells, total area of tumor cells has been reported as mean percentage of CD8+cells per unit area. Area was measured in millimeter square (mm^2).
Time Frame
From first dose of study drug up to end of treatment (maximum up to 20 months)
Title
Summary of Cluster of Differentiation 8 (CD8+) Cells Expression: Total Area Covered by CD8+ Cells in Center of Tumor Cells
Description
CD8+ cells are the type of T-lymphocytes.
Time Frame
From first dose of study drug up to end of treatment (up to 20 months)
Title
Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Positive Neutralizing Antibodies (nAbs)
Description
ADA positive was defined as presence of at least one positive ADA sample. nAb positive was defined as presence of at least one positive nAb sample.
Time Frame
From first dose of study drug until 30 days after the last dose of study drug (maximum up to 21 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Aichi Cancer Center Hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
464-8681
Country
Japan
Facility Name
Iizuka Hospital
City
Iizuka
State/Province
Fukuoka
ZIP/Postal Code
820-8505
Country
Japan
Facility Name
Kindai University Hospital, Department of Gastroenterology and Hepatology
City
Osaka-Sayama
State/Province
Osaka
ZIP/Postal Code
589-8511
Country
Japan
Facility Name
National Cancer Center Hospital
City
Chuo-ku
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
Kyorin University Hospital, Department of Medical Oncology
City
Mitaka-shi
State/Province
Tokyo
ZIP/Postal Code
181-8611
Country
Japan
Facility Name
Japanese Red Cross Musashino Hospital
City
Musashino
State/Province
Tokyo
ZIP/Postal Code
180-8610
Country
Japan
Facility Name
National Hospital Organization Kyushu Medical Center
City
Fukuoka
ZIP/Postal Code
810-8563
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=B9991024
Description
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Learn more about this trial
A Study Of Avelumab In Combination With Axitinib In Advanced HCC (VEGF Liver 100)
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