Atezolizumab/bevacizumab followed by on-demand TACE or initial synchronous treatment with TACE and atezolizumab/bevacizumab
- Conditions
- nresectable hepatocellular carcinoma (HCC)MedDRA version: 21.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002430-36-DE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 106
1.Patient’s signed informed consent
2.Age = 18 years at time of signing Informed Consent Form
3.Ability to comply with the study protocol, according to investigator's judgement
4.Life expectancy of at least 12 weeks
5.HCC with histologically confirmed diagnosis
6.Disease that is not amenable to curative surgical and/or local ablation treatment according to consensus resolution of the multidisciplinary tumor board of the trial center but eligible for TACE, with tumor burden below 50% of liver volume.
7.At least one measurable (per RECIST 1.1) untreated lesion
8.ECOG Performance Status of 0 or 1
9.Child-Pugh class A or B7
10.Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to randomization, unless otherwise specified:
–ANC =1.5 x 109/L (1500/µL) without granulocyte colony-stimulating factor support
–Lymphocyte count = 0.5 x 109/L (500/µL)
–Platelet count = 75 x109/L (75,000/µL) without transfusion
–Hemoglobin = 90 g/L (9 g/dL); patients may be transfused to meet this criterion.
–AST, ALT, and alkaline phosphatase = 5 x upper limit of normal (ULN)
–Serum bilirubin = 3 x ULN
–Serum creatinine = 1.5 x ULN or creatinine clearance = 50 mL/min (calculated using the Cockcroft-Gault formula)
–Serum albumin = 28 g/L (2.8 g/dL)
–For patients not receiving therapeutic anticoagulation: INR <1.25
–Urine dipstick for proteinuria < 2+ (within 14 days prior to initiation of study treatment), unless a subsequent 24-hour urine collection demonstrates < 1 g of protein in 24 hours.
11.Negative HIV test at screening
12.Documented virology status of hepatitis, as confirmed by screening HBV and HCV serology test.
For patients with active hepatitis B virus (HBV): HBV DNA < 500 IU/mL obtained within 28 days prior to randomization, and Anti-HBV treatment (per local standard of care) for a minimum of 14 days prior to randomization and willingness to continue treatment for the length of the study
13.For females of childbearing potential (FCBP): negative pregnancy test within 14 days before randomization and 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 or 6 months after the last dose of bevacizumab.
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 partner’s 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.
14.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
1.Diffuse HCC or presence of vascular invasion or extrahepatic spread or more than 7 lesions or at least one lesion = 7 cm
2. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
3. Clin. rel. ascites (defined by protocol)
4. Uncontrolled pleural Effusion/ pericardial effusion.
5. History or presence of hepatic encephalopathy
6. Co-infection of HBV and HCV
(History of HCV infection but negative for HCV RNA by PCR are considered non-infected with HCV)
7.Patients act. listed for transplantation or not yet listed but potentialy eligible for Transplantation (see protocol)
8.Prior systemic therapy for HCC
9.Prior treatment with TACE or SIRT
10.Prior local ablation treatment (refer to protocol for Detail)
11.Any contraindication to TACE
12.Major gastrointestinal bleeding within last 4 weeks
13.Patients with untreated or incompletely treated varices with bleeding or high-risk for bleeding (please refer to protocol)
14.Active or history of autoimmune disease or immune deficiency (described in protocol)
15.Prior allogeneic stem cell or solid organ transplantation
16.History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening CT scan (more Details in Protocol)
17.Active tuberculosis (defined by protocol)
18.Severe infection within last 4 weeks
19.Significant cardiovascular disease (more Details in protocol)
20.History of congenital long QT syndrome or corrected QT interval >500 ms or repeated demonstration of a corrected QT interval >450 ms
21.Inadequately controlled arterial hypertension (defined by protocol)
22.Significant vascular disease including aortic aneurysm requiring surgical repair or peripheral arterial thrombosis with last 6 months
23.History of abdominal or tracheoesophageal fistula or gastrointestinal perforation, or intra-abdominal abscess within last 6 months
24.History or clinical signs of gastrointestinal obstruction or requirement for routine parenteral Hydration/nutrition, or tube feeding. Evidence of abdominal free air (not explained by paracentesis/recent surgical procedure)
25.History of intra-abdominal inflammatory process within last 6 months
26.Evidence of bleeding diathesis or significant coagulopathy
27.Any other conditions that contraindicates participation in the sstudy
28.Uncontrolled tumor-related pain.
29.Severe, non healing or dehisced wound, active ulcer, or untreated bone fracture
30.History of malignancy other than HCC (with the exception: please refer to protocol)
31.Current or recent use of acetylsalicyclic acid or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol
32.Current or recent use of full dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose(for exeptions please refer to protocol)
33.Chronic daily treatment with NSAID. Occasional use of NSAIDs for the symptomatic relief is allowed.
34.Treatment with a live, attenuated vaccine within 4 weeks prior to randomization, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab.
35.Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti?CTLA-4, anti?PD-1, and anti?PD-L1 therapeutic antibodies
36.Hypersensitivity to atezolizumab, bevacizumab, any of the excipients, known hypersensitivity to CHO cell products or to human or humanized a
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of up-front atezolizumab/ bevacizumab (Atezo/Bev) followed by on-demand selective transarterial chemoembolization (sdTACE) and of initial synchronous treatment with TACE and Atezo/Bev in the treatment of unresectable HCC patients.;Secondary Objective: To evaluate the efficacy, safety and quality of life of treatment with Atezo/Bev in combination with TACE;Primary end point(s): To evaluate the efficacy of up-front atezolizumab/ bevacizumab (Atezo/Bev) followed by on-demand selective transarterial chemoembolization (sdTACE) and of initial synchronous treatment with TACE and Atezo/Bev in the treatment of unresectable HCC patients<br>Corresponding primary endpoint: Objective response rate (according to RECIST v1.1) (as assessed by local investigator) (ORR);Timepoint(s) of evaluation of this end point: Objective response rate will be evaluated continiously
- Secondary Outcome Measures
Name Time Method