Study of Bavituximab, Axitinib, and Avelumab in Advanced Hepatocellular Carcinoma

NCT05249569 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: STU-2022-0116
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Across cancer types, immune checkpoint inhibitors have been shown to induce complete response, partial response, and stable disease after initial evidence of radiographic increase in tumor burden. Treatment beyond progression should be considered when the patient is stable (or improving) symptomatically and if tumor reassessment can be performed within a short period.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Response Rate of Combination Therapy

  To determine the objective response rate of combination axitinib,avelumab, and bavituximab in advanced HCC not previously treated with systemic therapy.

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 24 months.

Secondary Outcomes (6)

• Disease Control Rate

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 48 months.

• Overall Survival

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 48 months.

• 6-month Progression-free Survival

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 48 months.

• Duration of Response

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 48 months.

• Safety Profile as Measured by the Number of Participants With AEs (Serious / Non-serious) as Graded by NCI CTCAE v5.0

  Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason up to 48 months.

Study Arms (1)

Axitinib / Avelumab /Bavituximab

EXPERIMENTAL

Axitinib 5 mg PO BID Avelumab 10 mg/kg IV every 2 weeks (2 doses in a 4-week cycle) Bavituximab 3 mg/kg IV every 1 week (4 doses in a 4-week cycle) Study treatment will continue until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.

Drug: Axitinib; Drug: Avelumab; Drug: Bavituximab

Interventions

Axitinib DRUG

Axitinib to be administered orally BID

Axitinib / Avelumab /Bavituximab

Avelumab DRUG

Avelumab to be administered as a 1-hour IV infusion on Day 1 and Day 15 of each 28-day cycle.

Axitinib / Avelumab /Bavituximab

Bavituximab DRUG

Bavituximab to be administered weekly on Days 1, 8, 15 and 22 of the 28-day cycle.

Axitinib / Avelumab /Bavituximab

Eligibility Criteria

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

You may qualify if:

• Patient must have a histologically confirmed diagnosis consistent with HCC; known fibrolamellar HCC, or combined HCC-cholangiocarcinoma will be excluded.
• Locally advanced or metastatic disease
• Patients with locally advanced or metastatic disease must have disease deemed not amenable to surgical and/or locoregional therapies or patients who have progressed following surgical and/or locoregional therapies.
• Measurable disease, as defined as lesions that can accurately be measured in at least one dimension according to RECIST version 1.1 at least 1 cm with contrast enhanced dynamic imaging (magnetic resonance imaging or computed tomography).
• Availability of recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or slides (biopsied tumor lesion should not be a RECIST target lesion): 1) the biopsy or resection was performed within 2 years of AND 2) the patient has not received any intervening systemic anti-cancer treatment from the time the tissue was obtained.
• Prior therapy is allowed provided the following are met: at least 4 weeks since prior locoregional therapy including surgical resection, chemoembolization, definitive radiotherapy with intent of disease control, or ablation. Provided target lesion has increased in size by 25% or more or the target lesion was not treated with locoregional therapy. Patients treated with palliative radiotherapy for symptoms will be eligible as long as the target lesion is not the treated lesion and radiotherapy will be completed at least 2 weeks prior to study drug administration.
• Age ≥ 18 years
• Child-Pugh Score A
• ECOG Performance score of 0-1
• Adequate organ and marrow function as defined below:
• Platelet count ≥ 50,000/mm3
• Hgb ≥ 8.5 g/dl
• Absolute neutrophil ≥ 1,500 cells/mm3
• Total bilirubin ≤ 2.0 mg/ml
• INR ≤ 1.7

You may not qualify if:

• Prior liver transplant.
• Prior systemic therapy directed at advanced or metastatic HCC.
• Prior immunotherapy with IL-2, or anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
• Prior therapy with axitinib or any prior therapies with other VEGF pathway inhibitors.
• Clinically significant, uncontrolled heart disease and/or recent events including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening).
• History of documented congestive heart failure (New York Heart Association functional classification III-IV).
• History of cerebrovascular accident, transient ischemic attack, deep vein thrombosis, or pulmonary embolism within 6 months of screening.
• Patient has a left ventricular ejection fraction \<40% as determined by MUGA scan or ECHO (MUGA and ECHO are not required prior to enrollment).
• Known human immunodeficiency virus (HIV) positive (testing not required).
• History of cerebrovascular accident, transient ischemic attack, or thromboembolic events (including both pulmonary embolism and deep venous thrombus but not including tumor thrombus) within the last 6 months.
• Hypersensitivity to IV contrast; not suitable for pre-medication.
• Active or fungal infections requiring systemic treatment within 7 days prior to screening.
• Known history of, or any evidence of, interstitial lung disease or active noninfectious pneumonitis.
• Evidence of poorly controlled hypertension which is defined as systolic blood pressure \>159 mmHg or diastolic pressure \>99 mmHg despite optimal medical management.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Pfizer: collaborator

Study Sites (1)

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Axitinib; avelumab; bavituximab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver 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: Dr. David Hsieh
• Organization: UT Southwestern Medical Center

david.hsieh@utsouthwestern.edu

214/648-4180

Study Officials

• David Hsieh, MD

  Assistant Professor

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Assistant Professor, Internal Medicine

Study Record Dates

• First Submitted: February 3, 2022
• First Posted: February 21, 2022
• Study Start: November 4, 2022
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2022
• Last Updated: May 3, 2023
• Results First Posted: May 3, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)