DYNAmic immune Microenvironment of HCC treated with atezolIzumab and bevaCizumab

Not Applicable

Recruiting

• Conditions: Neoplasms

• Registration Number: KCT0006281
• Lead Sponsor: Asan Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 2 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

Part I
1. Acquisition of Signed Informed Consent Form prior to any study specific procedures
2. Willingness and ability to comply with the study protocol
3. = 19 years of age at the time of signing Informed Consent Form
4. Eastern Cooperative Oncology Group (ECOG) performance status of =1
5. Histologically confirmed HCC or clinical diagnosis of HCC according to AASLD guideline
6. Child-Pugh class A (Child-Pugh score of 5 or 6) assessed within 7 days
7. Negative HIV test at screening
8. 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 initiation of study treatment, and Anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study
9. Potentially resectable Barcelona Clinic Liver Cancer (BCLC) stage B/C meeting any of the following criteria by 4-phase liver dynamic computed tomography (CT) or gadoxetic-acid enhanced magnetic resonance imaging (MRI) or chest CT with enhancement
-Portal vein invasion (Vp1, Vp2 and Vp3)
-Hepatic vein invasion (Vv1 and Vv2)
-Lymph node metastasis
-multiple tumor nodules (n = 2)
-Solitary distant metastasis
or
Resectable HCC meeting any of the following criteria by 4-phase liver dynamic CT or gadoxetic-acid enhanced MRI
-Serum alpha-feto protein (AFP) level of = 400ng/mL
-Largest tumor diameter of = 5cm
-Presence of satellite nodules

10. Presence of = 1 measurable untreated lesion (per RECIST v1.1)
11. One or more lesions should be accessible for biopsy
12. Adequate major organ functions as following:
-Hematopoietic function: absolute neutrophil count (ANC) ? 1,500/mm3, Platelet ? 75,000/mm3
-Hemoglobin ? 90 g/L (9 g/dL). Patients may be transfused to meet this criterion.
-Serum albumin ? 28 g/L (2.8 g/dL) without transfusion
-Hepatic function: serum bilirubin 2 x ULN, AST/ALT levels 5 x ULN
-Renal function: serum creatinine 1.5 x ULN or creatinine clearance ? 50 mL/min (calculated using the Cockcroft-Gault formula)
-Proteinuria: Urine dipstick for proteinuria ? 2+ (within 7 days prior to Day 1 of Cycle 1), patients discovered to have ? 2 ? proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate ? 1 g of protein in 24 hours.

13. PT INR < 1.5 or aPTT < 1.5 x ULN within 14 days prior to the start of study treatment for patients not receiving anti-coagulation. For patients receiving anticoagulants, INR and aPTT must be within the medical standard of enrolling institution.
14. 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 6 months after the last dose of study treatment after the last dose of study treatment.
15. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm during the treatment period and for 6months after the last dose of study treatment.
Part II
-Acquisition of Signed Informed Consent Form prior to any study specific procedures
-Histologically or cytologically confirmed HCC
-Eligible for surgical resection of liver
-= 19 years of age at the time of signing Informed C

Exclusion Criteria

Part I
1. Extrahepatic metastases that are not candidates for treatment of curative aim (e.g. resection, radiation or radiofrequency ablation)
2. Presence of central nervous system (CNS) metastases
3. Concurrent or previous history of another primary cancer within 3 years prior to study treatment except for curatively treated cervical cancer in situ, non-melanomatous skin cancer, superficial bladder cancer (pTis or pT1) and curatively treated thyroid cancer of any stage. Concurrent, histologically confirmed, unresected thyroid cancer without distant metastasis could be allowed with the agreement of the principal investigator.
4. Prior systemic therapy for metastatic disease including systemic investigational agents
5. Uncontrolled medical illness: including medically uncontrolled infection, uncontrolled hypertension, unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months
6. Current or recent (within 10 days of start of study treatment) use of aspirin (>325mg/day), clopidogrel (>75mg/day), oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes
(therapeutic anticoagulation on a stable dose for at least 2 weeks prior to the start of study treatment is allowed)
7. Known alcohol or drug abuse
8. 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
9. Treatment with therapeutic oral or IV antibiotics within 2 weeks 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.
10.Inadequately controlled hypertension (defined as systolic blood pressure >150mmHg and/or diastolic blood pressure >100mmHg)
11. Prior history of hypertensive crisis or hypertensive encephalopathy
12. History or evidence upon physical or neurological examination of CNS disease (e.g. seizures) unrelated to cancer unless adequately treated with standard medical therapy
13. Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of start of study treatment
14. 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), unstable arrhythmia, or unstable angina
15. Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
16. History of congenital long QT syndrome or corrected QT interval > 500 ms (calculated with use of Fridericia method) at screening
17. History of uncorrectable electrolyte disorder affecting serum levels of potassium, calcium, magnesium

18. Any previous venous thromboembolism > CTCAE Grade 3 within 12 months prior to start of study treatment
19. History of hemoptysis > CTCAE Grade 2 (= 2.5 mL of bright red blood per episode) within 1 month prior to initiation of study treatment
20. History of abdominal or trachoesophageal fistula, gastrointestinal perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to start of study treatment
21. Serious, non-healing wound, active ulcer, or untreated bone fracture
22. Known hype

Study & Design

• Study Type: Interventional Study
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The rate of pathological complete response (pCR) defined by the absence of viable tumor cells in any nodule. ;Distinct immunophenotypes and dynamic changes of tumor-infiltrating immune cells in HCCs treated with treated with atezolizumab–bevacizumab assessed by single nuclear RNA-sequencing, multiplexed immunohistochemistry (mIHC), flow cytometry (and/or CyTOF)