SAFETY AND EFFICACY OF ATEZOLIZUMAB PLUS BEVACIZUMAB COMPARED TO PLACEBO AFTER SELECTIVE INTERNAL RADIATION THERAPY IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA
- Conditions
- Neoplasms
- Registration Number
- KCT0009131
- Lead Sponsor
- ational Cancer Centre Singapore
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- All
- Target Recruitment
- 176
a) Unequivocal diagnosis of HCC (AASLD 2010 diagnostic criteria or histology) that is locally advanced without extra-hepatic metastases but with significant tumor burden, i.e.,
• Tumor confined to the liver that is beyond the up-to-7 criteria, and/or
• Tumor with vascular invasion VP 1-3 and/or Vv 1-2 (at the discretion of site investigator)
Both local and central assessments are required at screening, prior to any study treatment. Sites are required to send all CT/MRI images for central imaging review. The central assessment result will be made known to sites and will take precedence in determining a patient’s study eligibility in case of a discrepancy between local and central review.
b) Aged 21 years old and above of either gender.
c) Patient eligible for SIRT-Y90 treatment after assessment with macro-aggregated albumin labeled with technetium-99 (Tc-99m MAA) scan on SPECT/CT or planar imaging with all of the following criteria prior to each SIRT-Y90 treatment:
• Lung shunting <20% on SPECT/CT or planar imaging
• Lung dose limit of <25Gy for single treatment or <30Gy for cumulative treatment (second delivery within 4-6 weeks)
d) No prior radiation to the liver.
e) No prior systemic adjuvant or neoadjuvant therapy for HCC.
f) Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as =10 mm with spiral CT scan or MRI.
g) Negative HIV test at screening, with the following exception - patients with a positive HIV test at screening are eligible provided they fulfil all of the following criteria:
• Are stable on anti-retroviral therapy
• Have a CD4 count = 200/µL
• Have an undetectable viral load
h) Documented virology status of hepatitis, as confirmed by screening hepatitis B virus (HBV) and hepatitis C virus (HCV) tests.
i) Patients with active HBV: HBV DNA <500 IU/mL, 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).
For patients with HBV DNA = 500 IU/mL during screening, anti-HBV treatment will be initiated and HBV DNA levels will be re-assessed prior to randomization.
j) ECOG performance status 0 – 1.
k) Child-Pugh A (up to 6 points).
l) Adequate hematological, renal, and hepatic function as follows:
• Lymphocyte count = 0.5 × 10^(9)/L (500/µL)
• Platelets =75,000/µL without transfusion
• Hemoglobin >9.5 g/dL (Patients may be transfused to meet this criterion.)
• Serum bilirubin = 3 × ULN
• For patients not receiving therapeutic anticoagulation: INR and aPTT = 2.0 x ULN
• ALP =5×institutional upper limit of normal
• AST and ALT =5×institutional upper limit of normal
• Albumin = 2.8 g/dL
• Serum creatinine = 1.5 × ULN or creatinine clearance = 30 mL/min (calculated using the Cockcroft-Gault formula)
• Absolute Neutrophil Count = 1.5×10^(9)/L without granulocyte colony-stimulating factor support
• Urine dipstick for proteinuria <2+ at screening
o Patients discovered to have =2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate <1g of protein in 24 hours.
m) Life expectancy of at least 3 months without any active treatment.
n) Suitable for protocol treatment as determined by clinical assessment undertaken by the site investigator.
o) Performance of an esophagogastroduodenoscopy (EGD) within 6 months prior to randomizati
a) Patient not eligible for SIRT-Y90 treatment after assessment with macro-aggregated albumin labeled with technetium-99 (MAA) scan on SPECT/CT or planar imaging.
b) Patients who have SAE > grade 3 within 4 weeks after receiving SIRT-Y90.
For patients who experience SAE > grade 3 after receiving SIRT-Y90 (1st or 2nd administration), the duration between the SIRT-Y90 dose and randomization and/or 1st and 2nd SIRT-Y90 dose (for two-staged Y90 delivery) may be extended by an additional 4 weeks to re-assess the patient’s eligibility.
c) Patients who have had >2 administrations of hepatic artery directed therapy.
d) Patients who have had hepatic artery directed therapy done <4 weeks prior to date of ICF signing.
e) Patients who have had systemic adjuvant or neoadjuvant therapy for HCC.
f) Prior hepatic radiation therapy for HCC or other malignancy.
g) Patient who has received any immunotherapy (including interferon-alfa, peginterferon alfa-2a, peginterferon alfa-2b, thymosin-a1, etc.) within 30 days prior to randomization, is currently receiving immunotherapy or is planned to start immunotherapy during the study (e.g., for the management of active CHB or CHC according to local guidelines).
h) Has evidence that <30% of the total liver volume is disease-free.
i) Currently receiving any other investigational agents for the treatment of their cancer.
j) Has intractable clinical ascites (in spite of optimal diuretic treatment) or any other clinical signs of liver failure, on physical examination.
k) Untreated or incompletely treated esophageal and/or gastric varices prior to randomization.
l) Presence of tumor thrombus in the main trunk of the portal vein or a portal vein branch contralateral to the primarily involved lobe (or both) i.e. beyond VP337 and/or tumor thrombus in the inferior vena cava or right atrium i.e. beyond Vv2.
m) Any metastatic disease. In this context, local-regional lymph nodes measuring <2 cm in greatest diameter or lung nodules measuring <1 cm are not contraindications at the discretion of site investigator.
n) Any other concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least five years.
o) Presence of clinical signs of CNS metastases due to their poor prognosis and because progressive neurologic dysfunction would confound the evaluation of neurologic and other adverse events.
p) Uncontrolled inter-current illness including, but not limited to, ongoing or active infection (except viral hepatitis), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
q) Inadequately controlled arterial hypertension (defined as systolic blood pressure [BP]>150 mmHg and/or diastolic BP >100 mmHg), based on an average of at least three BP readings at two or more sessions.
• Anti-hypertensive therapy to achieve these parameters is allowed.
r) Any of the following contraindications to angiography and selective visceral catheterization:
• Bleeding diathesis, not correctable by the standard forms of therapy.
• Severe peripheral vascular disease that would preclude arterial catheterization.
s) Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months pr
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Best overall response rate
- Secondary Outcome Measures
Name Time Method Best overall response rate at 18 months;Sustained response rate at 12 and 18 months;Disease control rate at 12 and 18 months;Time to response;Time to disease progression;Progression-free survival (and rates at 12 and 18 months);Overall survival (and rates at 12 and 18 months);Health-related quality of life at 12 and 18 months;Quality-adjusted life years at 18 months;Safety profile