A Study Evaluating Atezolizumab and Bevacizumab Plus ADI-PEG 20 in Patients With Locally Advanced / Metastatic Hepatocellular Carcinoma

NCT06006286 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 2023-0208NCI-2023-06581
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

To learn about the safety and tolerability of atezolizumab, bevacizumab, and ADI-PEG 20 when given in combination to patients with locally advanced or metastatic liver cancer

Conditions

Metastatic Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year

Study Arms (1)

ADI-PEG20/ATEZO/BEV

EXPERIMENTAL

Participants will first receive the study drug combination for up to 12 weeks. If participants have stable disease or a partial response to the study drug after 12 weeks, participants may continue to receive ADI-PEG 20 for up to 2 years of total dosing, and participants may continue to receive atezolizumab and bevacizumab indefinitely (no limit)

Drug: Atezolizumab; Drug: Bevacizumab; Drug: ADI-PEG 20

Interventions

Atezolizumab DRUG

Given by IV (vein)

ADI-PEG20/ATEZO/BEV

Bevacizumab DRUG

Given by IV (vein)

ADI-PEG20/ATEZO/BEV

ADI-PEG 20 DRUG

Given by Injection (inj)

ADI-PEG20/ATEZO/BEV

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document for participation in this trial
• Willingness to sign a written informed consent document to participate in laboratory protocol PA13-0291 for the testing of biomarkers as described in this clinical protocol.
• ≥ 18 years of age
• Histologically confirmed HCC (documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable) or clinical diagnosis by AASLD (American Association for the Study for Liver Diseases) criteria in cirrhotic subjects (presence of nonrim arterial phase hyperenhancement relative to the liver parenchyma with venous washout for tumors \> 1 cm). For subjects without cirrhosis, histological confirmation is mandatory.
• The determination of cirrhosis status will ultimately lie in the clinical judgment of the surgical oncologist and medical oncologist involved in the care of the patient.
• Locally advanced or metastatic disease.
• Measurable disease defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures ≥ 15 mm with conventional techniques or ≥ 10 mm with more sensitive techniques such as magnetic resonance imaging (MRI) or spiral computed tomography (CT) scan.
• Eastern Cooperative Oncology Group performance status (ECOG PS) score ≤ 1.
• Child-Turcotte-Pugh Score A.
• Record of treated or absence of esophageal varices by esophagogastroduodenoscopy within 6 months of initiating treatment.
• Adequate organ and marrow function (as defined below) within 14 days of the first dose of study drug:
• Absolute neutrophil count ≥ 1,500/μL
• Platelets ≥100,000/μL
• Hemoglobin \> 9.0 g/dL (may be transfused or receive epoetin alfa \[e.g., Epogen®\] to maintain or exceed this level)
• Total bilirubin ≤ 1.5 x ULN with the following exception:

You may not qualify if:

• Any of the following criteria will disqualify the patient from participation:
• Any other malignancy from which the patient has been disease-free for less than 2 years (exceptions: non-melanoma skin cancer or in situ carcinoma of any site are allowed)
• Fibrolamellar HCC, sarcomatoid HCC, or hepatocellular cholangiocarcinoma
• Prior systemic therapy, anti-PD-1/PD-L1 or VEGF inhibitor or ADI-PEG 20 therapy.
• Note: Prior surgery, radiation therapy, or local-regional therapy (ablation or arterial directed therapies) are allowed.
• Receipt of organ allograft(s)
• Major surgical procedure, open biopsy, or significant traumatic injury with poorly healed wound within 6 weeks prior to first dose of study drug; or anticipates needing for a major surgical procedure during the course of the study (other than defined by protocol such as the pre-treatment fine needle aspirations or core biopsies) within 7 days prior to first dose of study drug.
• History of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) or a history of autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's granulomatosis\]).
• History of testing positive for human immunodeficiency virus or has acquired immunodeficiency syndrome (AIDS).
• Underlying medical condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or will obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea.
• Has a known risk factor for bowel perforation including a history of acute diverticulitis, abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or gastrointestinal obstruction.
• History of primary brain tumor (excluding meningiomas and other benign lesions), any brain metastases, leptomeningeal disease, seizure disorders not controlled with standard medical therapy, or (within the past year) a history of stroke.
• History of serious systemic disease, including myocardial infarction or unstable angina within the last 12 months; a history of hypertensive crisis or hypertensive encephalopathy, uncontrolled hypertension (systolic ≥ 150 mmHg and/or diastolic ≥ 100 mmHg at the time of enrollment); New York Heart Association (NYHA) Grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (patients with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible); significant vascular disease or symptomatic peripheral vascular disease.
• History of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
• History of seizure disorder not related to underlying cancer.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab; ADI PEG20

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)

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

Study Officials

• Zishuo (Ian) Hu, MD

  M.D. Anderson 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: SPONSOR

Study Record Dates

• First Submitted: August 17, 2023
• First Posted: August 23, 2023
• Study Start: August 8, 2023
• Primary Completion: November 10, 2023
• Study Completion: November 10, 2023
• Last Updated: August 26, 2024

Record last verified: 2024-08

Locations

US (1)