A Study to Evaluate Efficacy and Safety of Hepatic Resection for Liver Cancer With PVTT, HVTT or IVCTT After Initial Ate/Bev

NCT04649489 | Active Not Recruiting Phase 3

• 1 other identifier: ML42435
• Study Type: interventional
• Target: 501
• Locations: 1 country
• Sites: 23

Brief Summary

The treatment strategies for HCC with PVTT is still controversial, and differ substantially between the west and the east. According to western guidelines, including those of the EASL, BCLC, and AASLD, PVTT is regarded as a contra-indication to initial surgery or transarterial chemoembolization. At present, there is still no consensus on the diagnosis and treatment standards of HCC with HVTT/IVCTT. European and American guidelines for liver cancer use The Barcelona Clinic Liver Cancer (BCLC) staging as the standard and classify liver cancer with HVTT/IVCTT into the advanced stage. Molecular targeted drugs such as sorafenib and lenvatinib are recommended to the patients in this phase as first-line treatment drugs and methods. In this regard, experts in China and Southeast Asian countries still have different opinions. They believe that surgery, transarterial chemoembolization (TACE), radiotherapy, and combined treatment with multiple treatment methods can achieve more satisfactory results. HCC with VTT consists of heterogeneous populations with different disease behaviors and prognoses. As a result of recent concept evolution and advances in surgical techniques and perioperative management, emerging evidence shows that selected patients with PVTT may benefit from more aggressive treatment modalities, which are recommended for by Chinese, Japanese, South Korean, and Asia Pacific clinical practice guidelines. A national survey from Japan showed median overall survival with liver resection treatment to be 1.77 years longer than with nonresection therapies, which included TACE, radiotherapy, sorafenib, or conservative treatment (2.87 years vs 1.10 years, respectively; p\<0.001). After propensity-score matching of patient baseline characteristics, median overall survival since diagnosis in the liver resection group was 0.88 years longer than in the non-resection group. In a large-scale, multicentre, propensity-score matched analysis from China, surgery was the best treatment for patients with Cheng's type I and II PVTT with Child-Pugh A and selected B liver function. Median overall survival after liver resection (745 of 1580 patients) was 15.9 months (95% CI 13.3-18.5 months) for Cheng's type I PVTT and 12.5 months (10.7-14.3 months) for Cheng's type II PVTT. Thus, aggressive surgical resection in selected patients with HCC with vascular invasion, as proposed by several tertiary health-care centers in the east, seems to be reasonable. Currently, there are no dedicated clinical trials to study the value of hepatic resection in this population. Furthermore, cumulative evidence indicates that long-term overall survival after hepatic resection alone remains unsatisfactory because of the high rate of tumor recurrence and correspondingly low rate of disease-free survival. The combination of perioperative therapies may be more efficacious to improve the prognosis in selected population. More high-level evidence of novel multimodality treatment should be generated. This trial will enroll HCC patients with PVTT CNLC Stage IIIa, who have no prior anti-cancer treatment. Given the poor prognosis and limited treatment options for these patients, this population is considered appropriate for trials of more aggressive and novel therapeutic candidates in the initial treatment setting. The benefit risk profile for hepatic resection combined with perioperative atezo/bev in this patient population is expected to be favorable.

Conditions

Venous Thrombosis

Outcome Measures

Primary Outcomes (1)

• TTF

  Time-to-treatment failure (TTF) after randomization, defined as the time from randomization to the first documented treatment failure (i.e., local recurrence or progression, EHS, or death from any cause). Tumor response will be determined by the IRF according to RECIST v1.1

  24 months

Secondary Outcomes (5)

• OS

  24 months

• OS rate

  24 months

• TTF

  24 months

• TTF

  24 months

• Time to EHS

  24 months

Other Outcomes (6)

• AE/ADR

  24 months

• RFS

  24 months

• TTR

  24 months

Study Arms (2)

Arm A (experimental arm)

EXPERIMENTAL

hepatic resection with post-operative atezolizumab 1200mg and bevacizumab 15mg/kg, both administered by IV infusion on Day 1 of each 21-day cycle

Procedure: Surgery followed by atezolizumab and bevacizumab

Arm B (control arm)

ACTIVE COMPARATOR

atezolizumab 1200mg and bevacizumab 15mg/kg, both administered by IV infusion on Day 1 of each 21-day cycle

Drug: Atezolizumab & Bevacizumab

Interventions

Atezolizumab & Bevacizumab DRUG

atezolizumab 1200mg and bevacizumab 15mg/kg

Also known as: Bevacizumab

Arm B (control arm)

Surgery followed by atezolizumab and bevacizumab PROCEDURE

hepatic resection with post-operative atezolizumab 1200mg and bevacizumab 15mg/kg

Also known as: Atezolizumab, Bevacizumab

Arm A (experimental arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form (ICF)
• Aged ≥18 years at time of signing ICF
• Ability to comply with the study protocol, in the investigator's judgment
• Documented diagnosis of HCC confirmed by histology/cytology or clinically by AASLD criteria in cirrhotic patients - Patients without cirrhosis require histological confirmation of diagnosis.
• No prior anti-tumor treatment (including both local-regional and systemic therapies) for HCC
• Previous use of herbal therapies/traditional Chinese medicines (TCM) with anti-cancer activity included in the label is allowed, provided that these medications are discontinued at least 7 days prior to enrollment.
• Presence of PVTT, determined based on the radiological findings, including Vp1 (third-order branch of portal vein) to Vp4 (main trunk/collateral branch of portal vein) according to the Japanese staging system or Presence of HVTT or IVCTT, without atrium tumor thrombosis, determined based on the radiological findings
• Remnant liver volume-to-total liver volume (RLV%) ≥ 25%
• At least one measurable lesion (per RECIST v1.1) untreated lesion
• ECOG performance status of 0 or 1 within 7 days prior to study entry
• Child-Pugh class A within 7 days prior to study entry
• Life expectancy ≥12 weeks
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of induction treatment unless otherwise specified:
• \- Absolute neutrophil count (ANC)≥1.5x109/L (1500/uL) without granulocyte colony stimulating factor support
• \- Lymphocyte count ≥0.5x109/L (500/uL)

You may not qualify if:

• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Evidence of EHS, as confirmed by CT and/or MRI scans of the chest, abdomen, and pelvis
• Evidence of HCC disease progression or complete remission prior to randomization
• Clinically significant ascites
• History of hepatic encephalopathy
• 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 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 atezo/bev treatment do not need to repeat the procedure.
• 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, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroidreplacement 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 is 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 corticosteroids within the 12 months prior to Day 1 of Cycle 1.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan

Sponsors & Collaborators

• Jia Fan: lead

Study Sites (23)

Zhongshan hospital, Fudan University

Shanghai, Shanghai Municipality, 200000, China

Location

Beijing Cancer Hospital

Beijing, China

Location

Cancer Hospital Chinese Academy of Medical Science

Beijing, China

Location

Peking Union Medical College Hospital

Beijing, China

Location

Peking Univerty People's Hospital

Beijing, China

Location

Xiangya Hospital of Central South University

Changsha, China

Location

West China Hospital of Sichuan University

Chengdu, China

Location

Fujian Provincial Hospital

Fuzhou, China

Location

Mengchao Hepatobiliary Hospital of Fujian Medical University

Fuzhou, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, China

Location

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, China

Location

The Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, China

Location

Anhui Provincial Hospital

Hefei, China

Location

The Second Affiliated Hospital Kunming Medical University

Kunming, China

Location

The First Hospital of Lanzhou University

Lanzhou, China

Location

Jiangsu Provine People Hospital

Nanjing, China

Location

Guangxi Medical University Cancer Hospital

Nanning, China

Location

The First Affiliated Hospital Of Guangxi Medical University

Nanning, China

Location

Shanghai Jiao Tong University Ruijin Hospital

Shanghai, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjin, China

Location

Tongji Hospital of Tongji Medical College of HUST

Wuhan, China

Location

Henan Province People Hospital

Zhengzhou, China

Location

MeSH Terms

Conditions

Venous Thrombosis

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jia Fan

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Doctor of hospital

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: December 2, 2020
• Study Start: April 19, 2021
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: January 15, 2026

Record last verified: 2026-01

Locations

CN (23)