Trial of PXS-5505 Combined With First Line Atezolizumab Plus Bevacizumab For Treating Patients With Unresectable Hepatocellular Carcinoma

NCT05109052 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: SGIH21023
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This trial will assess the safety and tolerability of PXS-5505 incorporating first-line combination therapy Atezolizumab and Bevacizumab in unresectable or metastatic hepatocellular carcinoma. Phase 2 will assess the efficacy of this combination therapy in unresectable or metastatic hepatocellular carcinoma.

Conditions

Hepatocellular Carcinoma; Cancer of Liver

Keywords

Hepatocellular Carcinoma; Cancer of Liver; PXS-5505

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  measured by adverse event severity and quantity

  10 years

Study Arms (1)

Experimental

EXPERIMENTAL

Open label safety and tolerability assessment of PXS-5505: (PXS-5505) 100-200mg BID (Atezolizumab) 1200mg every 3 weeks (Bevacizumab) 15mg/kg every 3 weeks

Drug: PXS-5505 and Atezolizumab and Bevacizumab

Interventions

PXS-5505 and Atezolizumab and Bevacizumab DRUG

Open label safety and tolerability assessment of PXS-5505 incorporating first-line combination therapy Atezolizumab and Bevacizumab

Experimental

Eligibility Criteria

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

You may qualify if:

• Patient or legally authorized representative must be able to understand and willing to sign an IRB approved written informed consent document.
• Patients must be 18 years or older
• Patient must have histological or radiographically confirmed unresectable or metastatic hepatocellular carcinoma.
• Patients must have no concomitant active oncologic diagnosis
• Patient must have at least one radiographically measurable lesion defined as non-radiated lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 10mm with calipers by radiographic exam. Further details listed in section 5.5.
• Patient must have received no previous systemic or investigational therapy for the treatment of HCC. Patients who previously received locoregional therapies remain eligible for this study.
• Patient must have a life expectancy of minimum 3 months.
• Patient must have normal bone marrow and organ function as defined below.
• Absolute neutrophil count \>1,500/mcl
• Platelets \>75,000/ul without transfusion
• Hemoglobin \>9.0 g/dL
• Creatinine should be below the upper limit of normal OR
• Creatinine clearance \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Aspartate aminotransferase (AST), Alanine transaminase (ALT), and alkaline phosphatase (ALP) \<5 times the upper limit of normal
• Serum bilirubin no greater than 1.5-2x the upper limit of normal

You may not qualify if:

• Patient with any histologic variant of HCC such as fibrolamellar, sarcomatous, or mixed cholangiocarcinoma and HCC.
• Patient has a history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only, carcinoma in situ of the cervix, or prostate cancer that does not require treatment.
• Patient who received a previous systemic therapy for hepatocellular carcinoma or has tumor recurrence sooner than 6 months after completion of the last dose of therapy.
• Patient who is receiving any other investigational agent
• Patient has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXS-5505, Atezolizumab, or Bevacizumab
• Patient with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, any clinically active malabsorption syndrome, inflammatory bowel disease, any condition that increases the risk of severe gastrointestinal toxicity, or psychiatric illness/social situations that would limit compliance with study requirements
• Has current active autoimmune disease, or a documented history of autoimmune disease or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo, resolved childhood asthma/atopy, hypothyroidism on thyroid supplementation, and type 1 diabetics would be exception to this rule.
• Patients who are eligible for liver transplantation
• Has had an allogenic tissue/solid organ transplant.
• Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.
• Has received or plans to receive a live vaccine within 30 days prior to the first administration of study medication. Flu vaccines that do not contain live virus are permitted.
• Has known active Hepatitis B or C.
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding
• A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester

Rochester, New York, 14642, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nabeel Badri

  Univ. of Rochester Wilmot Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Instructor - Department of Medicine , Hematology/Oncology (SMD)

Study Record Dates

• First Submitted: September 15, 2021
• First Posted: November 5, 2021
• Study Start: September 20, 2022
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 13, 2023

Record last verified: 2023-07

Locations

US (1)