BridgeMD
New treatment option for Hepatocellular Carcinoma
Official title Atezolizumab and Bevacizumab in Combination With Y^90 Radioembolization in HCC for Liver Transplant
ClinicalTrials.gov ID: NCT07059494
What this study is testing
What is Atezolizumab?
Atezolizumab is an investigational medicine, being studied as a potential treatment for hepatocellular carcinoma.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- A single institution, single arm, two-cohort feasibility trial to evaluate the combination of locoregional Y\^90 therapy with systemic atezolizumab and bevacizumab, in participants presenting with hepatocellular carcinoma (HCC) 1) within Milan Criteria (MC) with AFP ≥ 400 ng/ml as a means of bridge therapy prior to transplant, 2) beyond the Milan Criteria (MC) (within USCF DS criteria and all comers), as a means of downstaging prior to liver transplantation.
- Phase 4: studies an already-approved treatment
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Signed Informed Consent Form
- Age ≥18 years at time of signing Informed Consent Form
- Ability to comply with the study protocol
- Newly diagnosed, biopsy-proven hepatocellular carcinoma (HCC) that is histologically or cytologically confirmed
- Availability of a representative tumor specimen that is suitable for determination of PD-L1 status via central testing. A formalin-fixed...
You likely can't join if
- AFP ≥ 1000 ng/ml
- Pathologically mixed tumors, vascular invasion or extra-hepatic disease based on cross-sectional imaging
- History of leptomeningeal disease
- Uncontrolled tumor-related pain o Participants requiring pain medication must be on a stable regimen at study entry.
- Severe pulmonary disease, uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or...
- Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN)
See the full eligibility criteria
Who can join
- Signed Informed Consent Form
- Age ≥18 years at time of signing Informed Consent Form
- Ability to comply with the study protocol
- Newly diagnosed, biopsy-proven hepatocellular carcinoma (HCC) that is histologically or cytologically confirmed
- Availability of a representative tumor specimen that is suitable for determination of PD-L1 status via central testing. A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or 10-15...
- Within MC with AFP ≥ 400 ng/ml
- single lesion (≤5cm) or 3 lesions (≤3cm)
- Absence of vascular invasion or extra-hepatic disease based on cross-sectional imaging
- Child-Pugh Score of A/B7 (without ascites)
- UNOS-DS Protocol
- HCC exceeding UNOS T2 criteria but meeting one of the following:
- Single lesion ≤ 8 cm
- 2 or 3 lesions each ≤ 5 cm with the sum of the maximal tumor diameters ≤8 cm
- or 5 lesions each ≤ 3 cm with the sum of the maximal tumor diameters ≤ 8 cm
- Absence of vascular invasion or extra-hepatic disease based on cross-sectional imaging
- Child-Pugh Score of A/B7 (without ascites)
- Beyond UNOS-DS Liver Only Protocol a. HCC exceeding UNOS-DS criteria by any of the following:
- HCC tumor number
- HCC tumor size
- Total HCC tumor diameter b. Absence of vascular invasion or extra-hepatic disease based on cross-sectional imaging c. Child-Pugh Score of A/B7 (without ascites)
- Measurable disease, or non-measurable but evaluable disease, per RECIST v1.1 criteria
- Must meet institutional standards for proteinuria (Urinalysis (pH, specific gravity, glucose, protein, ketones, and blood); dipstick permitted
- Eligible for treatment with Y\^90 and atezolizumab plus bevacizumab
- ECOG performance status of 0-1
- Life expectancy \> 6 months
- Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
- ANC 1.5 ≥ 10\^9/L (1500/µL) without granulocyte colony-stimulating factor support, with the following exception:
- Participants with benign ethnic neutropenia (BEN): ANC \< 1.3 x 10\^9/L (1300/μL) BEN (also known as constitutional neutropenia) is an inherited cause of mild or moderate neutropenia that is not associated with any...
- Lymphocyte count ≥ 0.5 x 10\^9/L (500/µL)
- Platelet count ≥ 100 x 10\^9/L (100,000/µL) without transfusion
- Hemoglobin ≥ 90 g/L (9 g/dL)
- Participants may be transfused to meet this criterion.
- AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 upper limit of normal (ULN)
- Serum bilirubin ≤ 1.5 x ULN with the following exception:
- Participants with known Gilbert disease: serum bilirubin ≤ 3 x ULN
- Serum creatinine ≤ 1.5 x ULN
- Serum albumin ≥ 25 g/L (2.5 g/dL)
- For participants not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN
- For participants receiving therapeutic anticoagulation: stable anticoagulant regimen
- Absent or controlled HIV, HCV, and HBV o Participants with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/μL, and have an undetectable viral load
- Negative serum pregnancy test within 14 days prior to the initiation of study treatment for participants of childbearing potential.
- Since adequate studies have not been performed in animals to determine whether Y\^90 affects fertility in males or females has teratogenic potential or has other adverse effects on the fetus, this product should not be...
- Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods
What rules you out
- AFP ≥ 1000 ng/ml
- Pathologically mixed tumors, vascular invasion or extra-hepatic disease based on cross-sectional imaging
- History of leptomeningeal disease
- Uncontrolled tumor-related pain o Participants requiring pain medication must be on a stable regimen at study entry.
- Severe pulmonary disease, uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) o Participants with indwelling catheters (e.g...
- Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN)
- Active or history of autoimmune disease or immune deficiency, including, but not limited to, uncontrolled HIV, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis...
- Participants with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
- Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
- Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., participants with psoriatic arthritis are excluded) are eligible for the study provided all of...
- Rash must cover \< 10 percent of body surface area
- Disease is well controlled at baseline and requires only low-potency topical corticosteroids
- There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or...
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed...
- Active tuberculosis
- Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 12 months prior to initiation of study treatment...
- Major surgical procedure, other than for diagnosis or standard HCC care, within 4-6 weeks prior to initiation of study treatment, or during the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to initiation of study treatment o Placement of a vascular access device should be at least 2 days...
- History of malignancy within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival (OS) rate \> 90 percent), such as adequately...
- Severe active infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, active infection requiring...
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment o Participants receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic...
- Prior allogeneic stem cell, solid organ, or multi-organ transplantation
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render...
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of...
- Treatment with investigational therapy within 28 days prior to initiation of study treatment
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study...
- Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation...
- Participants who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible...
- Participants who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal...
- 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 allergy or hypersensitivity to any component of the study therapy
- Prior locoregional or systemic therapy
- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 6 months after the final dose of study treatment.
- Inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg)
- History of hypertensive crisis or hypertensive encephalopathy
- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to randomization
- History of Grade ≥ 4 venous thromboembolism
- History or evidence upon physical or neurological examination of central nervous system involvement
- History of Grade ≥ 2 hemoptysis (defined as ≥ 2.5 mL of bright red blood per episode) within 1 month prior to screening
- History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation)
- History of abdominal fistula, GI perforation, intra-abdominal abscess, or active GI bleeding within 6 months prior to randomization
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- Current or recent (\ 325 mg/day), or clopidogrel (\> 75 mg/day) Note: The use of full-dose oral or parenteral anticoagulants for therapeutic purpose is permitted as long as the INR and/or aPTT is within therapeutic...
The study team makes the final eligibility decision.
Where it's taking place
- New York, New York, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include New York, New York, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.