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New treatment option for Hepatocellular Carcinoma
Official title Atezolizumab and Bevacizumab Pre-Liver Transplantation for Patients With Hepatocellular Carcinoma Beyond Milan Criteria
ClinicalTrials.gov ID: NCT05185505
What this study is testing
What is Atezolizumab?
Atezolizumab is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for hepatocellular carcinoma.
Also referred to as Tecentriq.
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
- Patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are transplant-eligible will be treated with 6 months of neoadjuvant/downstaging atezolizumab plus bevacizumab while receiving standard of care transarterial chemoembolization (TACE). We hypothesize that atezolizumab and bevacizumab can appropriately bridge patients with HCC beyond MC to transplantation and not increase the risk of 1-year post-transplant rejection.
- Phase 4: studies an already-approved treatment
- Which group you join is decided by chance.
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
- Male or female, aged ≥18 years old at the time of signing Informed Consent Form
- Measurable or evaluable disease per RECIST v1.1 or mRECIST of unresectable HCC outside of Milan criteria
- Histologically proven HCC, without extrahepatic disease. Patients who consent to a fresh tissue biopsy, and under the discretion of the...
- Prior remote LRT is allowed if new lesions or local disease recurrence are present
- Must be eligible for liver transplantation, defined in Section 10.4
You likely can't join if
- Known fibrolamellar HCC, sacromatoid HCC, or mixed cholangiocarcinoma and HCC
- Previous systemic therapy for HCC prior to study enrollment
- Planned or prior multi-organ transplant or prior solid organ or allogeneic stem cell transplantation
- History of Grade ≥4 venous thromboembolism
- History or evidence upon physical or neurological examination of central nervous system (eg seizures) unrelated to cancer unless adequately treated...
- Moderate or severe ascites
See the full eligibility criteria
Who can join
- Male or female, aged ≥18 years old at the time of signing Informed Consent Form
- Measurable or evaluable disease per RECIST v1.1 or mRECIST of unresectable HCC outside of Milan criteria
- Histologically proven HCC, without extrahepatic disease. Patients who consent to a fresh tissue biopsy, and under the discretion of the Investigators, will provide a baseline biopsy sample for diagnosis and correlative...
- Prior remote LRT is allowed if new lesions or local disease recurrence are present
- Must be eligible for liver transplantation, defined in Section 10.4
- Eligible and suited to receive TACE procedure(s)
- Child-Pugh score ≤A6
- Eastern Cooperative Oncology Group (ECOG) score 0-1
- Life expectancy of ≥ 6 months
- Adequate hematological and end-organ function, defined by the following laboratory test results obtained within 14 days prior to study initiation:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Lymphocyte count ≥ 0.5 x 10\^9/L (500/uL)
- Platelet count \> 75 x 109/L
- Hemoglobin \> 9 g/dL
- Total bilirubin \< 1.5 x upper limit of normal (ULN)
- Aspartate transaminase (AST),alanine aminotransferase (ALT), and alkaline phosphatase (ALP) \< 2.5 x ULN
- Serum albumin \> 2.7 g/dL
- Serum creatinine \< 1.5x ULN or calculated creatinine clearance \< 50 ml/min
- Urine dipstick for proteinuria ≥ 2+ unless a 24-hour urine protein \< 1 g of protein is demonstrated
- International normalized ratio (INR) ≤ 1.5 or partial thromboplastin time (PTT) ≤ 1.5 x ULN for patients not receiving anti-coagulation. The use of full-dose oral or parenteral anticoagulants is permitted as long as the...
- No evidence of a Grade 2 or higher esophageal and/or gastric varices. Patients must have an esophagogastroduodenoscopy (EGD) within 6 months prior to initiating the study treatment. See Section 8.7.1.2.
- No history of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month of study enrollment
- Negative HIV test at screening or transplant workup
- Negative hepatitis B surface antigen (HBsAg) test at screening or transplant workup
- Negative total hepatitis B core antibody (HBcAb) test at screening or transplant workup, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening or transplant workup. The HBV...
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, as defined below:
- Women must remain abstinent or use contraceptive methods with a failure rate of \<1% per year during the treatment period and for 6 months after the final dose of atezolizumab/bevacizumab Females who receive a LT are...
- A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not...
- Examples of contraceptive methods with a failure rate of \<1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and...
- The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation...
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:
- With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 6 months after the final dose of atezolizumab/bevacizumab to...
- The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation...
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Women of childbearing potential must have a negative serum or urine pregnancy test result within 14 days prior to initiation of study treatment.
What rules you out
- Known fibrolamellar HCC, sacromatoid HCC, or mixed cholangiocarcinoma and HCC
- Previous systemic therapy for HCC prior to study enrollment
- Planned or prior multi-organ transplant or prior solid organ or allogeneic stem cell transplantation
- History of Grade ≥4 venous thromboembolism
- History or evidence upon physical or neurological examination of central nervous system (eg seizures) unrelated to cancer unless adequately treated with standard medical therapy. Anticonvulsants (stable dose) are...
- Moderate or severe ascites
- History of hepatic encephalopathy
- 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 drug administration
- Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment...
- History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation)
- Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to initiation of study...
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device within 7 days prior to initiation of study treatment. Placement of a vascular access device should be at least 2 days prior...
- History of abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess, grade 2 or higher untreated esophageal or gastric varices or active GI bleeding within 6 months prior to treatment
- Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding. Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be...
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- Other malignancy within 5 years prior to randomization, except for localized cancer in situ, such as basal or squamous cell skin cancer
- 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 a PTT is within therapeutic...
- Pregnancy (positive pregnancy test) or lactation, or intention of becoming pregnant during study treatment or within 6 months after the final dose of study drugs o Women of childbearing potential must have a negative...
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- Patients with indwelling catheters (e.g., PleurX®) are allowed
- 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, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel...
- Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (eg, patients with psoriatic arthritis are excluded) are eligible for the study provided all following...
- Rash must cover \< 10% of body surface area
- Disease is well controlled at baseline and requires only low-potency topical corticosteroids
- 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 oral...
- History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed...
- Active tuberculosis
- 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 (e.g., FluMist®) 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...
- Current treatment with anti-viral therapy for HBV
- 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...
- Patients 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 for...
- Patients who received mineralocorticoids (eg, 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 allergy or hypersensitivity to any component of the Atezlizumab and Bevacizumab formulation, such as a known hypersensitivity to Chinese hamster ovary cell products
- Inability to comply with study and/or follow-up procedures
- Active infection requiring IV antibiotics within 2 weeks prior to initiation.
- Note: Placement of a vascular access device should be at least 2 days prior to initiation of study treatment.
- Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
- Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- History of leptomeningeal disease
- Evidence of abdominal free air that is not explained by paracentesis or recent surgical procedure
- History of intra-abdominal inflammatory process within 6 months prior to initiation of study treatment, including but not limited to active peptic ulcer disease, diverticulitits, or colitis.
- Chronic daily treatment with a nonsteroidal anti-inflammatory drug (NSAID). Occasional use of NSAIDs for the symptomatic relief of medical conditions such as headache or fever is allowed
- Uncontrolled tumor-related pain
- Patients requiring pain medication must be on a stable regimen at study entry.
- Symptomatic lesions (eg, bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation...
The study team makes the final eligibility decision.
Where it's taking place
- Houston, Texas, United States
Compensation & support
A stipend or compensation may be offered.
Compensation mentioned.
ClinicalTrials.gov doesn't provide a reliable structured field for payment or travel support - confirm details with the study team.
Questions & answers
Do participants get paid in this trial?
This study's listing includes signals that participants may be compensated or receive a stipend. Amounts vary and are set by the study team - confirm the details with them.
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 Houston, Texas, 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.