A randomized, multicenter, open-label, phase II trial of atezolizumab plus bevacizumab alone or combined with external radiation therapy in patients with macrovascular invasion of hepatocellular carcinoma
- Conditions
- Neoplasms
- Registration Number
- KCT0007365
- Lead Sponsor
- Asan Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 138
Patients must meet the following criteria for study entry:
Signed Informed Consent Form
Older than 19 years of age, lower than 80 years of age
Child-Pugh class A hepatic function
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
Patients with HCC [diagnosed according to AASLD guidelines] invading the intrahepatic vascular system
No prior systemic therapy for HCC, at least one measurable HCC lesion with = 1cm diameter
Adequate hematologic and organ function
- Hemoglobin = 9.0 g/dL
- Absolute neutrophil count = 1,000 /mm3
- Platelet = 100,000/ mm3 without transfusion
- Total bilirubin = 2.5 mg/dL
*Patients with known Gilbert disease: total bilirubin ? 3 ? ULN
- Albumin = 2.8 g/dL
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) = 5 x upper limit of normal (ULN)
- Prothrombin time international normalized ratio = 1.8
- Serum creatinine < 1.5 mg/dL
For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
Negative HIV test at screening, with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ? 200/uL, and have an undetectable viral load}
Documented virology status of hepatitis, as confirmed by screening HBV and HCV serology test
For patients with active hepatitis B virus (HBV): HBV DNA < 2000 IU/mL obtained within 28 days prior to initiation of study treatment, or Anti-HBV treatment (per local standard of care; e.g., entecavir, tenofovir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of <1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab, 6 months after the last dose of bevacizumab. Women must refrain from donating eggs during this same period.
– A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
– 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 copper intrauterine devices.
– 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 (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
– With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 6 months after the last dose of bevacizumab. Men must refrain from donating sperm during this same period.
– With pregnant female partners, men must remain abstinent or use a condom during the treatmen
Patients who meet any of the following criteria will be excluded from study entry:
Treatment history of prior systemic treatment, or radiotherapy primary of metastatic HCC or tumor thrombosis
Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
Asymptomatic patients with treated or untreated CNS lesions are eligible, provided that all of the following criteria are met:
– Measurable disease, per RECIST v1.1, must be present outside the CNS.
– The patient has no history of intracranial hemorrhage or spinal cord hemorrhage.
– The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment.
– The patient has no ongoing requirement for corticosteroids as therapy for CNS disease.
– If the patient is receiving anti-convulsant therapy, the dose is considered stable.
Uncontrolled ascites and hepatic encephalopathy
Active infectious condition
Patients with peptic ulcer, untreated or incompletely treated varices with bleeding or high-risk for bleeding
*Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Patients who have undergone an EGD within 6 months of prior to initiation of study treatment do not need to repeat the procedure.
History of liver transplantation
Any serious illness (e.g., active infection or inflammatory condition) or uncontrolled severe medical comorbidity
A history of treated malignancy (other than HCC) is allowable if the patient’s malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding two years
History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
Pregnant or breastfeeding women
Abdominal/pelvic radiotherapy within 28 days prior to initiation of study treatment, except palliative radiotherapy to bone lesions within 7 days prior to initiation of study treatment
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment
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 disease, anti phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis (see Appendix 2 for a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions:
Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
–Rash must cover ? 10% 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 u
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method progression-free survival
- Secondary Outcome Measures
Name Time Method overall survival;Objective response;Safety;Quality of life