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Metastatic Hepatocellular CarcinomaPhase 1/2NCT06006286

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

A Phase 1/2 study testing Atezolizumab, Bevacizumab and ADI-PEG 20 in people with Metastatic Hepatocellular Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Hepatocellular Carcinoma
What is being tested?
Atezolizumab, Bevacizumab and ADI-PEG 20
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
8 Aug 2023to 10 Nov 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • Patients with known Gilbert disease: serum bilirubin ≤ 3 x ULN
  • Estimated creatinine clearance >40mL/min.
  • Aspartate transaminase (AST) (SGOT) and/or alanine transaminase (ALT) (SGPT) ≤ 5 X institutional ULN
  • Documented virology status of hepatitis, as confirmed by screening HBV and HCV tests for patients with active HBV: HBV DNA ≤ 500 IU/mL during screening, initiation of anti-HBV treatment at least 14 days prior to randomization and willingness to continue anti-HBV treatment during the study (per local standard of care: e.g., entecavir)
  • UA with protein less than 2+
  • Serum uric acid ≤10 mg/dL (595 μmol/L) (with or without medication control).
  • Negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug and every 4 weeks while taking atezolizumab and bevacizumab (for women of childbearing potential [WOCBP]).
  • Not breastfeeding
  • The effects of ADI-PEG 20 on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men who are sexually active with WOCBP must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for a total of 12 (women) or 7 (men who are sexually active with WOCBP) months after the completion of API-PEG 20 (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
  • Postmenopausal (no menses in greater than or equal to 12 consecutive months).
  • History of hysterectomy or bilateral salpingo-oophorectomy.
  • Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
  • History of bilateral tubal ligation or another surgical sterilization procedure.
  • Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. NOTE: Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, WOCBP must still undergo pregnancy testing as described in these sections.

Who cannot join

  • 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)
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  • 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.
  • Known allergy to pegylated compounds.
  • Known allergy to E. coli drug products (such as granulocyte-macrophage colony stimulating factor).
  • Has had influenza-, hepatitis-, or other vaccines within a month prior to initiation of study drugs.
  • Has had a clinical history of coagulopathy, bleeding diathesis or thrombosis within the past year.
  • Significant pulmonary disease including tuberculosis, pneumonia, pneumonitis, etc.
  • Requires recurrent drainage procedures including pleural effusion, ascites, etc.
  • Surgical procedure within 6 weeks of initiation of study treatment.
  • History of severe allergic/anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
  • Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation.
  • Known hypersensitivity to bevacizumab.
  • Receipt of investigational agents within 28 days prior to initiation of study treatment.
  • History of severe infection within 4 weeks of initiation of treatment.
  • Receipt of stem cell transplantation, liver transplantation, or solid organ transplantation
  • Serious, non-healing wound, ulcer, or bone fracture.
  • Patient is pregnant (positive pregnancy test) or lactating.
  • Prior orthotropic liver transplantation.
  • Prohibited therapies and/or medications:
  • Prior anticancer therapy with ADI-PEG 20 or anti-VEGF or anti-PD-1/PD-L1 for HCC. Must not be receiving any concomitant systemic therapy for HCC
  • Complementary medications (e.g., herbal supplements or traditional Chinese medicines) intended to treat the disease under study unless patients agree to stop the complementary medicines at least 14 days before the first study dose. Such medications are permitted if they are used as supportive care.
  • Live / attenuated vaccine (e.g., varicella; zoster; yellow fever; rotavirus; oral polio; or and measles, mumps, rubella) within a month prior to initiation of study drug or during treatment.
  • Any other experimental drug while on this study.
  • Ongoing anticoagulation therapy (although aspirin is permitted).
  • total parenteral nutrition.
  • high dose steroid (e.g., > 10 mg prednisone daily or equivalent) or other more potent immune suppression medications (e.g., infliximab).
  • Inability to comply with the appointments required in this protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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

Read the detailed description

Primary Objectives:

--To evaluate the safety and tolerability of treatment with atezolizumab and bevacizumab + ADI-PEG 20 in Patients with Locally Advanced/ Metastatic Hepatocellular Carcinoma.

Secondary Objectives:

--To assess the pathologic response rate including pathologic complete response (pCR) per RECIST and degree of necrosis (>50% in tumor volume) with atezolizumab and bevacizumab + ADI-PEG 20 in treatment-naïve locally advanced or metastatic HCC.

Exploratory Objectives:

--To assess the immunological/biomarker changes (pre- vs. post-treatment) in tumor tissues and peripheral blood in response to atezolizumab and bevacizumab + ADI-PEG 20 in HCC therapy and explore any potential association between these biomarker measures and antitumor response.

Being tested
Atezolizumab, Bevacizumab, ADI-PEG 20
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT06006286
Study groupRoleWhat they receive
ADI-PEG20/ATEZO/BEVExperimentalParticipants 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)
Receives: Drug: Atezolizumab; Drug: Bevacizumab; Drug: ADI-PEG 20

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: through study completion; an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Aug 2023
  2. Study start8 Aug 2023
  3. Primary completion10 Nov 2023
  4. Study completion10 Nov 2023

Why it stopped: 0 participants registered

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06006286
Sponsor's protocol ID
2023-0208
Other IDs
NCI-2023-06581
Status last verified
Aug 2024
First submitted
17 Aug 2023
Last updated
26 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Atezolizumab, Bevacizumab and ADI-PEG 20 in people with Metastatic Hepatocellular Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 26 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 (time frame: through study completion; an average of 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06006286.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2024.

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