A Study Of Avelumab In Combination With Axitinib In Advanced HCC (VEGF Liver 100)

NCT03289533 | Completed Phase 1 Results

• 1 other identifier: B9991024
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 7

Brief Summary

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

Conditions

Carcinoma, Hepatocellular

Keywords

Cancer; Hepatocellular carcinoma; Liver disease; Avelumab; Axitinib

Outcome Measures

Primary Outcomes (3)

• 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.

  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)

• 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.

  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)

• 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.

  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 (15)

• Time to Disease Progression (TTP)

  From first dose of study drug until first documentation of progressive disease or data censoring date, whichever occurred first (maximum up to 20 months)

• Progression Free Survival (PFS)

  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)

• Percentage of Participants With Objective Response (OR)

  From first dose of study drug until disease progression or death due to any cause (maximum up to 20 months)

• Percentage of Participants With Disease Control (DC)

  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)

• Time to Tumor Response (TTR)

  From first dose of study drug until first documentation of CR or PR (maximum up to 20 months)

Study Arms (1)

Experimental 1

EXPERIMENTAL

Avelumab (MSB0010718C) in combination with axitinib (AG-013736)

Drug: Avelumab (MSB0010718C); Drug: Axitinib (AG-013736)

Interventions

Avelumab (MSB0010718C) DRUG

Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID.

Experimental 1

Axitinib (AG-013736) DRUG

Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID.

Experimental 1

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (7)

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, 464-8681, Japan

Location

Iizuka Hospital

Iizuka, Fukuoka, 820-8505, Japan

Location

Kindai University Hospital, Department of Gastroenterology and Hepatology

Ōsaka-sayama, Osaka, 589-8511, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Kyorin University Hospital, Department of Medical Oncology

Mitaka-shi, Tokyo, 181-8611, Japan

Location

Japanese Red Cross Musashino Hospital

Musashino, Tokyo, 180-8610, Japan

Location

National Hospital Organization Kyushu Medical Center

Fukuoka, 810-8563, Japan

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Neoplasms; Liver Diseases

Interventions

avelumab; Axitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2017
• First Posted: September 21, 2017
• Study Start: September 8, 2017
• Primary Completion: August 27, 2019
• Study Completion: October 25, 2019
• Last Updated: September 4, 2020
• Results First Posted: September 4, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

JP (7)