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

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ClinicalTrials.gov Identifier: NCT03289533
Recruitment Status : Completed
First Posted : September 21, 2017
Last Update Posted : November 15, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

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

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Drug: Avelumab (MSB0010718C) Drug: Axitinib (AG-013736) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: AN OPEN LABEL, SINGLE ARM PHASE 1B STUDY OF AVELUMAB PLUS AXITINIB AS FIRST LINE TREATMENT IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA
Actual Study Start Date : September 8, 2017
Actual Primary Completion Date : August 27, 2019
Actual Study Completion Date : October 25, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental 1
Avelumab (MSB0010718C) in combination with axitinib (AG-013736)
Drug: Avelumab (MSB0010718C)
Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID.

Drug: Axitinib (AG-013736)
Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID.




Primary Outcome Measures :
  1. Adverse events (AEs) and laboratory abnormalities as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03. [ Time Frame: Until 90 calendar days after the last administration of study treatment ]

Secondary Outcome Measures :
  1. Time to Progression (TTP) [ Time Frame: Every 8 weeks up to 16 months. ]
    TTP is the time from the start date to the date of the first documentation of objective progression of disease (PD).

  2. Overall Survival (OS) [ Time Frame: Every 30 days (up to 90 days after the last administration) and then every 3 months up to 5 years ]
  3. Maximum plasma concentration (Cmax) of avelumab [ Time Frame: 1 hour post-dose ]
  4. Maximum plasma concentration (Cmax) of axitinib [ Time Frame: 2 hour post-dose ]
  5. Tumor tissue biomarker status (ie, positive or negative based on, for example, PD-L1 expression and/or quantitation of tumor infiltrating CD8+ T lymphocytes as assessed by immunohistochemistry [IHC]). [ Time Frame: Pre-dose ]
  6. Anti drug antibodies (ADAs, neutralizing antibodies [nAbs]) for avelumab when in combination with axitinib. [ Time Frame: Pre-dose ]
  7. Progression Free Survival (PFS) [ Time Frame: Every 8 weeks up to 16 months. ]
    PFS is the time from the start date to the date of the first documentation of objective progression of disease (PD) or death due to any cause.

  8. Objective Response (OR) [ Time Frame: Every 8 weeks up to 16 months. ]
    Number of participants with objective response (ie, confirmed complete or partial response according to RECIST Version 1.1) from the start date until disease progression or death due to any cause.

  9. Time to Tumor Response (TTR) [ Time Frame: Every 8 weeks up to 16 months. ]
    TTR is the time from start date to the first documentation of objective tumor response (CR or PR) that is subsequently confirmed.

  10. Duration of Response (DR) [ Time Frame: Every 8 weeks up to 16 months. ]
    DR is the time from the first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the first documentation of objective tumor progression or to death due to any cause.

  11. Trough plasma concentration (Ctrough) of avelumab [ Time Frame: Pre-dose ]
  12. Trough plasma concentration (Ctrough) of axitinib [ Time Frame: Pre-dose ]
  13. Disease Control (DC) [ Time Frame: Every 8 weeks up to 16 months. ]
    DR is the time from the first documentation of objective tumor response (CR or PR) that is subsequently confirmed to the first documentation of objective tumor progression or to death due to any cause.



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03289533


Locations
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Japan
Aichi Cancer Center Hospital
Nagoya, Aichi, Japan, 464-8681
Iizuka Hospital
Iizuka, Fukuoka, Japan, 820-8505
Kindai University Hospital, Department of Gastroenterology and Hepatology
Osaka-Sayama, Osaka, Japan, 589-8511
National Cancer Center Hospital
Chuo-ku, Tokyo, Japan, 104-0045
Kyorin University Hospital, Department of Medical Oncology
Mitaka-shi, Tokyo, Japan, 181-8611
Japanese Red Cross Musashino Hospital
Musashino, Tokyo, Japan, 180-8610
National Hospital Organization Kyushu Medical Center
Fukuoka, Japan, 810-8563
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03289533     History of Changes
Other Study ID Numbers: B9991024
First Posted: September 21, 2017    Key Record Dates
Last Update Posted: November 15, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Cancer
Hepatocellular carcinoma
Liver disease
Avelumab
Axitinib
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Axitinib
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action