Hepatocellular CarcinomaPhase 1/2ToripalimabNCT04926532
Toripalimab Plus Sorafenib in Patients With Advanced-Stage Hepatocellular Carcinoma
A Phase 1/2 study testing Toripalimab and Sorafenib in people with Hepatocellular Carcinoma, run by Shanghai Zhongshan Hospital at 1 site in China.
Trial summary
Toripalimab is a programmed cell death protein 1 antibody.This is an open-label, single arm, multi-center exploratory study.The objective of this study is to evaluate the efficacy and safety of therapy with toripalimab and sorafenib in patients with advanced stage hepatocellular carcinoma. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Toripalimab and Sorafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2019to 31 Dec 2021
- Phase
- Phase 1/2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject age: 18-75 years old, male or female;
- Hepatocellular carcinoma diagnosis confirmed by imaging, histopathology or cytology (fibrous layer and mixed hepatocyte/cholangiocarcinoma subtype do not meet the inclusion criteria).
- According to the clinical stage of Chinese liver cancer (2017 edition), the stage is stage II b or III, and one of the following conditions is met: (1) patients with hepatocellular carcinoma who cannot undergo surgical resection; (2) are unwilling to undergo surgical resection or arterial Patients with hepatocellular carcinoma treated with chemoembolization (TACE).
- Child-Pugh liver function scores were grade A or B within 7 days prior to the first dose of study drug.
- Laboratory tests must meet the following criteria within 7 days of starting treatment:
- Neutrophils ≥1.5 × 109/L;
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- platelets ≥ 50 × 109 / L;
- hemoglobin ≥ 90g / L (not infused with concentrated red blood cells within 2 weeks);
- serum creatinine ≤ 1.5 upper limit of normal (ULN) and creatinine clearance ≥ 50ml / min;
- aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN;
- serum albumin ≥ 30g / L;
- Patients who did not receive anticoagulant therapy: INR ≤ 1.5 × ULN. If the patient receives prophylactic anticoagulant therapy, the INR ≤ 2 × ULN within 14 days before the start of the study treatment and the activated partial thromboplastin time is within the normal range, acceptable for enrollment;
- serum bilirubin ≤ 1.25 × ULN;
- Life expectancy is >3 months.
- Confirm that there is at least one measurable lesion based on the RECIST 1.1 standard.
- The Physical Status (PS) score of the Eastern Cooperative Oncology Group (ECOG) was 0-1 within 7 days prior to the first dose of study drug.
- Male subjects must agree to take contraceptives during treatment and at least 120 days after the last study drug administration, and during this time no sperm can be donated.
- Female subjects must not be pregnant, not breastfeeding, and at least one of the following conditions can be included in the study: women who do not have fertility or who agree to be at least 120 days after the treatment and the last study drug administration Fertility women who take contraceptive measures as required by the programme.
- Subject (or legal representative, if applicable) provides informed consent to participate in the study.
- Subjects with previous or persistent hepatitis C virus (HCV) infection will be eligible to participate in the study. Subjects who are treated must complete treatment at least 1 month before starting the study treatment.
- Controlled hepatitis B subjects are eligible to participate in the study as long as they meet the following criteria: The HBV viral load must be less than or equal to 10,000 IU/mL prior to the first study drug administration. Subjects receiving anti-HBV therapy with a viral load of less than or equal to 10,000 IU/mL should maintain the same treatment throughout the study treatment period. Anti-hepatitis B core antibody HBc positive, hepatitis B surface antigen (HBsAg) negative, anti-hepatitis B surface antibody (HBsAb) negative or positive, and subjects with HBV viral load below 10000 IU/mL do not need anti- HBV prophylactic treatment.
- Blood pressure (BP) range of ≤150/90 mm Hg with or without antihypertensive drugs, and the qualification of subjects receiving ≥4 antihypertensive drugs prior to the study will require approval by the sponsor.
- Subjects have normal organ function, such as thyroid function, pituitary function, and bone marrow function.
- Specimens must be collected within 7 days prior to initiation of study treatment.
Who cannot join
- Esophageal or gastric varices bleeding occurred in the past 6 months.
- There is a bleeding or thrombotic disease or use an X-factor inhibitor or anticoagulant, such as warfarin or similar, that requires monitoring of the International Normalized Ratio (INR). Treatment with low molecular weight heparin is permitted. Antiplatelet drugs were banned throughout the study.
- Clinically significant ascites that was not controlled by drugs when examined. (Note: Ascites found only through imaging examinations is allowed to participate in the study)
- According to imaging examination, there is a tumor thrombus invasion, inferior vena cava or cardiac involvement at the portal vein (Vp4).
- It has been clinically diagnosed as hepatic encephalopathy in the past 6 months. Subjects with hepatic encephalopathy controlled with rifaximin or lactulose are not allowed to participate in the study.
- There are medical contraindications that do not accept any contrast-enhanced imaging (CT or MRI).
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- Existing ≥ 3 gastrointestinal or non-gastrointestinal fistulas.
- Clinically significant hemoptysis or tumor hemorrhage for any cause within 2 weeks prior to the first dose of study drug.
- Major cardiovascular damage within 12 months prior to the first dose of study drug: a history of congestive heart failure, grade II or older, unstable angina, myocardial infarction, or cerebrovascular accident, or with the New York Heart Association (NYHA) Arrhythmias associated with hemodynamic instability.
- Suffering from severe unhealed wounds, ulcers or fractures.
- Previously received any surgery, intervention, radiotherapy, systemic chemotherapy, targeted therapy, anti-PD-1 and anti-PD-L1 antibodies and Chimeric Antigen Receptor T-Cell Immunotherapy and other immunotherapy.
- Vaccines were administered within 30 days prior to the first dose of study drug. Live vaccines include, but are not limited to, measles, mumps, rubella, varicella/herpes (chickenpox), yellow fever, rabies, Bacillus Calmette Guerin, and typhoid vaccine. Since the seasonal influenza vaccine for injection is usually an inactivated virus vaccine, it is allowed to be used; however, an intranasal influenza vaccine (for example, FluMist) is a live attenuated vaccine and is therefore not allowed.
- Currently participating in or previously participating in a trial drug study, or using a test device within 4 weeks prior to the first dose of the study drug. Note: Subjects who have entered the clinical trial follow-up period may participate in this trial, provided that the last trial is administered 4 weeks after the last dose of the drug.
- Diagnosis of immunodeficiency or long-term systemic steroid therapy (daily dose over 10 mg prednisone equivalent) or any form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Another malignant tumor is known and is currently undergoing progress or has been actively treated in the past 3 years. Note: Subjects who have received skin basal cell carcinoma, cutaneous squamous cell carcinoma, or carcinoma in situ (eg, breast cancer, cervical cancer in situ) that may be curable may be treated.
- A known history or any evidence of central nervous system (CNS) metastasis and/or cancerous meningitis, as assessed by local research center researchers.
- Those who are severely allergic to research interventions and/or any of their excipients (≥3).
- Active autoimmune diseases (ie, immunomodulatory drugs, corticosteroids, or immunosuppressive drugs) that require systemic therapy in the past 2 years. Autoimmune diseases such as autoimmune hepatitis, interstitial pneumonia, Uveitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid syndrome-related vascular thrombosis, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barré syndrome, multiple sclerosis, Angiitis, glomerulonephritis, etc., hyperthyroidism or hypothyroidism, asthma requiring bronchodilator treatment, etc., immunomodulatory drugs, corticosteroids or immunosuppressive drugs). Alternative treatments (eg, thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) are not considered systemic and are permitted.
- Clinically significant liver diseases are known, including active viral hepatitis, alcoholic hepatitis or other hepatitis, severe cirrhosis, fatty liver, hereditary liver disease, liver atrophy, portal hypertension, uncontrollable major seizures or Superior vena cava syndrome; for unexplained liver disease, after eliminating viral infection, alcohol and other reasons, it is required to detect autoimmune antibodies and exclude autoimmune liver disease.
- Active viral hepatitis is defined as: HBV infection with hepatitis B virus DNA (HBV DNA) > 10000 cps/mL; or HCV infection;
- Patients with previous HBV infection or HBV infection who have been cured [defined as hepatitis B virus core antibody (HBcAb) positive and hepatitis B virus surface antigen (HBsAg) negative] may participate in this study. In the first 28 days before administration, the HBV DNA test results of this type of patients must be ≤ 10000 cps/mL;
- Patients with positive HCV antibody test results can only be included in the study when the results of polymerase chain reaction (PCR) detection of hepatitis C virus ribonucleic acid (HCV RNA) are negative.
- The study enrolled with dual active HBV infection (HBsAg (+) and/or detectable HBV DNA) and HCV infection (anti-HCV Ab(+) and detectable HCV RNA.
- There were dual active HBV infections and hepatitis D virus infections at the time of enrollment.
- There is a history of (non-infectious) pneumonia requiring steroid therapy or current pneumonia.
- Urine test strips Subjects with proteinuria >1+ will receive 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urinary protein ≥1 g/24 h were not eligible.
- Correct QT (QTc) interval extension > 480ms (Fridericia formula correction).
- Left ventricular ejection fraction (LVEF) measured by multi-gate acquisition scan (MUGA) or echocardiography (ECHO) is below the normal range of the mechanism.
- Active infections that require systemic therapy, with the exception of HBV and HCV.
- A history of human immunodeficiency virus (HIV) infection is known. HIV testing is not required unless mandatory by local health authorities.
- History of active tuberculosis (Bacillus tuberculosis).
- It is possible to interfere with the test results, the history of the disease or disease evidence, treatment or laboratory values that interfere with the subject's full participation in the study, or the investigator believes that participating in the study is not in the best interest of the subject.
- Known mental illness or substance abuse conditions can impede the ability of the subject to meet research requirements.
- During the study period, from the screening visit until 120 days after the last dose of the trial treatment, pregnancy or lactation, or planning to become pregnant or become a father.
- Subjects who have received allogeneic tissue/solid organ transplantation.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Zhongshan Hospital
Shanghai
Jian Zhou, Professor, 021 64037181, zhou.jian@zs-hospital.sh.cn
About this study
Official title: An Open-label, Single Arm, Multi-center Pilot Study of Programmed Cell Death Protein 1 Antibody (PD-1# Toripalimab Combined With Sorafenib in Patients With Advanced Hepatocellular Carcinoma Cannot Undergo Surgical Resection and TACE
Toripalimab is a programmed cell death protein 1 antibody.This is an open-label, single arm, multi-center exploratory study.The objective of this study is to evaluate the efficacy and safety of therapy with toripalimab and sorafenib in patients with advanced stage hepatocellular carcinoma.
Read the detailed description
The objective of this study is to evaluate the efficacy and safety of therapy with toripalimab and sorafenib in patients with advanced stage hepatocellular carcinoma.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Toripalimab, Sorafenib
- Keywords
- Toripalimab
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToripalimabDrug
Toripalimab is a humanized anti-PD-1 monoclonal antibody
SorafenibDrug
Sorafenib is a multi-kinase inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Toripalimab + Sorafenib | Experimental | Toripalimab was administered intravenously at a fixed dose of 240 mg, and the infusion time was 60 ± 5 min, once every 21 days. The cumulative longest medication period is 2 years. Sorafenib was taken orally after meals, twice a day. Receives: Drug: Toripalimab; Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
The proportion of patients in this trial whose tumor is destroyed or significantly reduced by the treatment. The extent of the reduction is assessed by researchers based on the RECIST 1.1 standard.
Measured: through study completion, an average of 1 year
Secondary outcomes (4)
Progression free survival (PFS)
The length of time during and after the treatment, that a patient lives with the tumor but it does not get worse.
Measured: through study completion, an average of 1 year
Disease Control Rate (DCR)
The percentage of patients who have achieved complete response, partial response and stable disease after treatment.
Measured: through study completion, an average of 1 year
Duration of relief (DOR)
The length of time that a tumor continues to respond to treatment without the cancer growing or spreading.
Measured: through study completion, an average of 1 year
Overall survival
Evaluated by patients' survival status
Measured: 10 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2021
- Study start1 Aug 2019
- Primary completion31 Oct 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Zhongshan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jian Zhou, Professor, Study director, Shanghai Zhongshan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04926532
- Sponsor's protocol ID
- ZSGW-PD1-sora
- Acronym
- Toripalimab
- Status last verified
- May 2021
- First submitted
- 9 Oct 2019
- Last updated
- 15 Jun 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single Arm, Multi-center Pilot Study of Programmed Cell Death Protein 1 Antibody (PD-1# Toripalimab Combined With Sorafenib in Patients With Advanced Hepatocellular Carcinoma Cannot Undergo Surgical Resection and TACE
- ClinicalTrials.gov ID
- NCT04926532
- Acronym / sponsor ID
- Toripalimab / ZSGW-PD1-sora
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Toripalimab
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Shanghai Zhongshan HospitalUniversity, hospital or other
- Study start
- 1 Aug 2019 (actual)
- Primary completion
- 31 Oct 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 15 Jun 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.
Toripalimab is a programmed cell death protein 1 antibody.This is an open-label, single arm, multi-center exploratory study.The objective of this study is to evaluate the efficacy and safety of therapy with toripalimab and sorafenib in patients with advanced stage hepatocellular carcinoma.
Detailed description
The objective of this study is to evaluate the efficacy and safety of therapy with toripalimab and sorafenib in patients with advanced stage hepatocellular carcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Toripalimab + Sorafenib | Experimental | Drug: Toripalimab, Drug: SorafenibToripalimab was administered intravenously at a fixed dose of 240 mg, and the infusion time was 60 ± 5 min, once every 21 days. The cumulative longest medication period is 2 years. Sorafenib was taken orally after meals, twice a day. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Subject age: 18-75 years old, male or female;
- Hepatocellular carcinoma diagnosis confirmed by imaging, histopathology or cytology (fibrous layer and mixed hepatocyte/cholangiocarcinoma subtype do not meet the inclusion criteria).
- According to the clinical stage of Chinese liver cancer (2017 edition), the stage is stage II b or III, and one of the following conditions is met: (1) patients with hepatocellular carcinoma who cannot undergo surgical resection; (2) are unwilling to undergo surgical resection or arterial Patients with hepatocellular carcinoma treated with chemoembolization (TACE).
- Child-Pugh liver function scores were grade A or B within 7 days prior to the first dose of study drug.
- Laboratory tests must meet the following criteria within 7 days of starting treatment:
Key exclusion criteria (35 listed)
- Esophageal or gastric varices bleeding occurred in the past 6 months.
- There is a bleeding or thrombotic disease or use an X-factor inhibitor or anticoagulant, such as warfarin or similar, that requires monitoring of the International Normalized Ratio (INR). Treatment with low molecular weight heparin is permitted. Antiplatelet drugs were banned throughout the study.
- Clinically significant ascites that was not controlled by drugs when examined. (Note: Ascites found only through imaging examinations is allowed to participate in the study)
- According to imaging examination, there is a tumor thrombus invasion, inferior vena cava or cardiac involvement at the portal vein (Vp4).
- It has been clinically diagnosed as hepatic encephalopathy in the past 6 months. Subjects with hepatic encephalopathy controlled with rifaximin or lactulose are not allowed to participate in the study.
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 |
|---|---|---|
| ToripalimabToripalimab is a humanized anti-PD-1 monoclonal antibody | Drug | Toripalimab + Sorafenib |
| SorafenibSorafenib is a multi-kinase inhibitor | Drug | Toripalimab + Sorafenib |
Primary outcome
Objective response rate (ORR)
Time frame: through study completion, an average of 1 year
The proportion of patients in this trial whose tumor is destroyed or significantly reduced by the treatment. The extent of the reduction is assessed by researchers based on the RECIST 1.1 standard.
4 secondary outcomes
Progression free survival (PFS)
Time frame: through study completion, an average of 1 year
Disease Control Rate (DCR)
Time frame: through study completion, an average of 1 year
Duration of relief (DOR)
Time frame: through study completion, an average of 1 year
Overall survival
Time frame: 10 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2021.
- Individual participant dataSharing planned: Undecided
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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.
Jian Zhou, Professor study director
Shanghai Zhongshan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Toripalimab and Sorafenib in people with Hepatocellular Carcinoma, run by Shanghai Zhongshan Hospital at 1 site in China.
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 24 inclusion and 35 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 15 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Contact Jian Zhou, Professor (021 64037181, zhou.jian@zs-hospital.sh.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jun 2021.