Hepatocellular Carcinoma With Major Portal Vein ThrombosisPhase 2NCT04947826

Combination Therapy of HAIC and HLX10 and HLX04 in HCC With Major Portal Vein Tumor Thrombosis

A Phase 2 study testing HAIC (Hepatic arterial infusion chemotherapy), HLX10 (PD-1 antibody) and HLX04 (VEGF antibody) in people with Hepatocellular Carcinoma With Major Portal Vein Thrombosis, run by Shanghai Zhongshan Hospital.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial summary

This is a randomized, double-blinded, controlled, phase II study. The purpose is to evaluate efficacy and safety of the combination therapy of HAIC (Hepatic arterial infusion chemotherapy) with HLX10 (PD-1 antibody) and HLX04 (VEGF antibody) compared with HAIC and placebo in patients with hepatocellular carcinoma with… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hepatocellular Carcinoma With Major Portal Vein Thrombosis
What is being tested?: HAIC (Hepatic arterial infusion chemotherapy), HLX10 (PD-1 antibody) and HLX04 (VEGF antibody)
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 100 participants
Where: No sites listed yet
Study dates: Aug 2021to Jul 2024
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Willing to attend the study and having given the ICF
Age ≥18
Have a HCC diagnosis confirmed by radiology, histology, or cytology
HCC is diagnosed at Barcelona Clinic Liver Cancer (BCLC) Stage C with major portal vein tumor thrombosis ( VP3～4, or Cheng's II～IV)
Have not accepted any of systemic therapy for HCC such as systemic chemotherapy, molecular targeted drugs, immunotherapy.
At least 1 measurable intrahepatic lesion suitable for repeat assessments according to RECISTv1.1 criteria and it has not undergone surgery, radiology and/or other regional therapy (including but not limited to radiofrequency ablation, percutaneous ethanol injection, freezing therapy, high intensity focused ultrasound, transcatheter arterial chemoembolization, transcatheter arterial embolization). But if it progressed after the regional therapy, it could be selected as a target lesion. The local regional therapy must be done 4 weeks before randomization and the related AEs must recover to ≤ CTCAE grade 1.

Show all 12Show fewer

Child-Pugh score ≤7
Eastern Cooperative Oncology Group (ECOG) 0 or 1
Expected life time is over 12 weeks.
HBV-DNA < 2000 IU/mL
Organs function:
Platelet count ≥75×109/L Absolute neutrophil count (ANC) ≥1.5×109 /L White blood cell count ≥3.0×109 /L Haemoglobin ≥9.0 g/dL Serum total bilirubin ≤1.5×ULN ALT ≤5×ULN, and AST ≤5×ULN（ALT ≤3×ULN, and AST ≤3×ULN, if HCV-RNA is detectable） Albumin ≥28 g/L INR ≤1.5×ULN PT ≤1.5×ULN APTT ≤1.5×ULN Creatinine clearance (CL) >50 mL/min or serum creatinine ≤1.5×ULN Urine protein ≤1+ or ≤1.0g/24h 12. Patient is not fertile or willing and able to obey effective contraception.

Who cannot join

Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC
History of hepatic encephalopathy
History of GI bleeding within 6 months, or investigator defined with high risk of haemorrhage for esophageal varices
With distant metastasis (hilar lymph nodes metastasis is allowed)
Co-infection of HBV and HCV
History of other malignancy within 5 years except for healed local tumor.

Show all 28Show fewer

History of or plan to accept allogenic organ transplantation
Ascites requiring invasive intervention (e.g. paracentesis) to maintain symptomatic control (every month or more often)
History of myocardial infarction or unstable angina or uncontrolled arrythmia or stroke or cerebral hemorrhage within 6 months prior to randomization. QTcF value ≥450ms（male）or ≥470ms（female） detected by 12-lead electrocardiogram.
New York Heart Association Grade ≥2 congestive heart failure or LVEF <50%
Uncontrolled hypertension
History of hypertensive crisis or hypertensive encephalopathy
Active infection including but not limited to tuberculosis and HIV
With interstitial lung disease, lung fibrosis, pneumoconiosis, radiation pneumonitis, drug-associated pneumonia and serious impairment in lung function
Active autoimmune disorders except patients with substitutional treatment with thyroid hormone and type I diabetes under treatment with insulin.
Receipt of live attenuated vaccine within 28 days prior to randomization
Current or prior use of steroids (>10mg/d prednisone) or immunosuppressive medication within 14 days before randomization
Significant traumatic injury or major surgical procedure within 28 days prior to randomization
Receipt of checkpoint inhibitors or T cell costimulatory drugs
Receipt of bevacizumab or its analogues
Involved in another clinical trial less than 14 days before randomization
Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control
Active bleeding, with history of ≥grade 3 bleeding within 6 months, or ≥grade 2 bleeding within 3 months
Use of anti-thrombotics within 5 days prior to randomization
In need of NSAIDs for long-term treatment.
With one of the following diseases within 6 months before randomization:
Digestive fistula, perforation and abscess (2) Gastrointestinal obstruction (3) Abdominal infection or inflammation (4) Major vascular disease 28. With severe and green wound, active ulcer or untreated fracture 29. History of drug abuse 30. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to screen for the study

About this study

Official title: A Randomized, Double-blinded, Controlled Phase II Study of Combination Therapy of HAIC (Hepatic Arterial Infusion Chemotherapy), HLX10 (PD-1 Antibody) and HLX04 (VEGF Antibody) Compared With HAIC and Placebo in Hepatocellular Carcinoma With Major Portal Vein Tumor Thrombosis

Conditions: Hepatocellular Carcinoma With Major Portal Vein Thrombosis
Being tested: HAIC (Hepatic arterial infusion chemotherapy), HLX10 (PD-1 antibody), HLX04 (VEGF antibody), Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

HAIC (Hepatic arterial infusion chemotherapy)Procedure or surgery
For the HAIC procedure, a 5F catheter was introduced using the Seldinger technique through the femoral artery or the radial artery. Then, angiographic surveys of the celiac trunk and superior mesenteric artery were performed. According to tumor size, location, and arterial supply, the catheter or a 2.7F microcatheter was advanced into the hepatic artery at the level of selective segmental, lobar, or whole liver. The catheter or microcatheter was connected to an external infusion pump. The following regimen of modified FOLFOX was administered: oxaliplatin, 85mg/m2 for 2 hours; leucovorin, 400mg/m2; and 5-fluorouracil, 2400mg/m2 for 44-46 hours. After HAIC treatment, the catheter or microcatheter, and the sheath were removed.
HLX10 (PD-1 antibody)Drug
PD-1 antibody with proven efficacy in advanced hepatocellular carcinoma
HLX04 (VEGF antibody)Drug
Combination of PD-1 antibody and VEGF antibody might promote the efficacy of HAIC in hepatocellular carcinoma with major portal vein thrombosis.
PlaceboDrug
Placebo

Study groups in NCT04947826
Study group	Role	What they receive
HAIC + HLX10 + HLX04	Experimental	HAIC: FOLFOX, q3w, up to 8 times; HLX10: 4.5mg/kg, iv, q3w, up to 2 years; HLX04: 15.0mg/kg, iv, q3w, up to 2 years. Receives: Procedure: HAIC (Hepatic arterial infusion chemotherapy); Drug: HLX10 (PD-1 antibody); Drug: HLX04 (VEGF antibody)
HAIC + Placebo	Placebo comparator	HAIC: FOLFOX, q3w, up to 8 times; Placebo1: saline, iv, q3w, up to 2 years; Placebo2: saline, iv, q3w, up to 2 years. Receives: Procedure: HAIC (Hepatic arterial infusion chemotherapy); Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Objective response rate
efficacy
Measured: The proportion of patients with complete response or partial response, through study completion, an average of 3 years.

Secondary outcomes (7)

Progression free survival
efficacy
Measured: From date of randomization until the date of the first documented progression or date of death from any cause, whichever comes first, up to 48 months
Duration of response
efficacy
Measured: From date of randomization until the date of first documented progression, up to 48 months
Time to response
efficacy
Measured: From date of randomization until the date of first documented response, up to 48 months
Time to progression
efficacy
Measured: From date of randomization until the date of first documented progression, up to 48 months
Overall survival
efficacy
Measured: From date of randomization until death from any cause, up to 48 months
Progression free survival rate at 12-month time point
efficacy
Measured: From date of randomization until 12-month time point
Overall survival rate at 12-month time point
efficacy
Measured: From date of randomization until 12-month time point

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2021Jul 2024

First posted1 Jul 2021
Study startAug 2021 (estimated)
Primary completionJul 2024 (estimated)
Study completionJul 2024 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Hepatocellular Carcinoma With Major Portal Vein ThrombosisStudies of the same condition, open and under way.
More trials run by Shanghai Zhongshan HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 100 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04947826
Sponsor's protocol ID: HHH
Status last verified: Jun 2021
First submitted: 18 Jun 2021
Last updated: 1 Jul 2021
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 1 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-blinded, Controlled Phase II Study of Combination Therapy of HAIC (Hepatic Arterial Infusion Chemotherapy), HLX10 (PD-1 Antibody) and HLX04 (VEGF Antibody) Compared With HAIC and Placebo in Hepatocellular Carcinoma With Major Portal Vein Tumor Thrombosis
ClinicalTrials.gov ID: NCT04947826
Acronym / sponsor ID: HHH
Conditions: Hepatocellular Carcinoma With Major Portal Vein Thrombosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 100 participants (estimated)
Lead sponsor: Shanghai Zhongshan HospitalUniversity, hospital or other
Collaborators: Shanghai Henlius Biotech
Study start: Aug 2021 (estimated)
Primary completion: Jul 2024 (estimated)
Study completion: Jul 2024 (estimated)
First posted: 1 Jul 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
HAIC + HLX10 + HLX04	Experimental	Procedure: HAIC (Hepatic arterial infusion chemotherapy), Drug: HLX10 (PD-1 antibody), Drug: HLX04 (VEGF antibody)HAIC: FOLFOX, q3w, up to 8 times; HLX10: 4.5mg/kg, iv, q3w, up to 2 years; HLX04: 15.0mg/kg, iv, q3w, up to 2 years.
HAIC + Placebo	Placebo comparator	Procedure: HAIC (Hepatic arterial infusion chemotherapy), Drug: PlaceboHAIC: FOLFOX, q3w, up to 8 times; Placebo1: saline, iv, q3w, up to 2 years; Placebo2: saline, iv, q3w, up to 2 years.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Willing to attend the study and having given the ICF
Age ≥18
Have a HCC diagnosis confirmed by radiology, histology, or cytology
HCC is diagnosed at Barcelona Clinic Liver Cancer (BCLC) Stage C with major portal vein tumor thrombosis ( VP3～4, or Cheng's II～IV)
Have not accepted any of systemic therapy for HCC such as systemic chemotherapy, molecular targeted drugs, immunotherapy.

Key exclusion criteria (28 listed)

Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC
History of hepatic encephalopathy
History of GI bleeding within 6 months, or investigator defined with high risk of haemorrhage for esophageal varices
With distant metastasis (hilar lymph nodes metastasis is allowed)
Co-infection of HBV and HCV

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
HAIC (Hepatic arterial infusion chemotherapy)For the HAIC procedure, a 5F catheter was introduced using the Seldinger technique through the femoral artery or the radial artery. Then, angiographic surveys of the celiac trunk and superior mesenteric artery were performed. According to tumor size, location, and arterial supply, the catheter or a 2.7F microcatheter was advanced into the hepatic artery at the level of selective segmental, lobar, or whole liver. The catheter or microcatheter was connected to an external infusion pump. The following regimen of modified FOLFOX was administered: oxaliplatin, 85mg/m2 for 2 hours; leucovorin, 400mg/m2; and 5-fluorouracil, 2400mg/m2 for 44-46 hours. After HAIC treatment, the catheter or microcatheter, and the sheath were removed.	Procedure or surgery	HAIC + HLX10 + HLX04, HAIC + Placebo
HLX10 (PD-1 antibody)PD-1 antibody with proven efficacy in advanced hepatocellular carcinoma	Drug	HAIC + HLX10 + HLX04
HLX04 (VEGF antibody)Combination of PD-1 antibody and VEGF antibody might promote the efficacy of HAIC in hepatocellular carcinoma with major portal vein thrombosis.	Drug	HAIC + HLX10 + HLX04
PlaceboPlacebo	Drug	HAIC + Placebo

Primary outcome

Objective response rate
Time frame: The proportion of patients with complete response or partial response, through study completion, an average of 3 years.
efficacy

7 secondary outcomes

Progression free survival
Time frame: From date of randomization until the date of the first documented progression or date of death from any cause, whichever comes first, up to 48 months
Duration of response
Time frame: From date of randomization until the date of first documented progression, up to 48 months
Time to response
Time frame: From date of randomization until the date of first documented response, up to 48 months
Time to progression
Time frame: From date of randomization until the date of first documented progression, up to 48 months
Overall survival
Time frame: From date of randomization until death from any cause, up to 48 months
Progression free survival rate at 12-month time point
Time frame: From date of randomization until 12-month time point
Overall survival rate at 12-month time point
Time frame: From date of randomization until 12-month time point

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2021.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 1 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (time frame: The proportion of patients with complete response or partial response, through study completion, an average of 3 years.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04947826.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2021.