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Unresectable Hepatocellular CarcinomaPhase 2NCT05214339

A Trial of Hepatic Arterial Infusion Combined With Bevacizumab and Sintilimab for Unresectable A-staged Hepatocellular Carcinoma in BCLC Classification (D-TRIPLET)

A Phase 2 study testing Hepatic Arterial Infusion(mFOLFOX7) combined with Bevacizumab and Sintilimab in people with Unresectable Hepatocellular Carcinoma and Hepatocellular Carcinoma by BCLC Stage, run by Sun Yat-sen University at 5 sites in China.

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 The sponsor has not verified this record for over two years, so it may be out of date.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

Trial summary

This study was designed to evaluate the effectiveness and safety of hepatic arterial infusion chemotherapy combined with Bevacizumab and Sintilimab (Triplet-combined Therapy) for Unresectable A-staged Hepatocellular Carcinoma in BCLC classification. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Hepatic Arterial Infusion(mFOLFOX7) combined with Bevacizumab and Sintilimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
5 sitesChina
Study dates
16 Mar 2022to 1 Jun 2023
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The patient voluntarily joins the study and signs an informed consent;
  • Age≥18 years old, ≤70 years old, both men and women;
  • Clinical or pathologically confirmed unresectable BCLC A-stage hepatocellular carcinoma, no further anti-tumor treatment;
  • Child-Pugh score small or equal to 6 points (Child-Pugh A-B);
  • ECOG score: 0 to 1 (according to the ECOG score classification);
  • The expected survival is longer than 12 weeks;
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  • The laboratory parameters meets the following requirements (no blood components and cell growth factors are allowed within 14 days before the first dose):
  • Absolute neutrophil count≥3.0×109 / L;
  • Platelets≥80×109 / L;
  • Hemoglobin≥90 g / L;
  • serum albumin≥28 g / L;
  • Thyroid stimulating hormone (TSH)≤1×ULN (if abnormalities should be considered at the same time FT3, FT4 levels, patients with FT3 and FT4 levels in normal range can also be enrolled);
  • bilirubin≤1.5×ULN (within 7 days prior to the first dose);
  • ALT≤3 x ULN and AST≤3 x ULN (within 7 days prior to the first dose);
  • AKP≤2.5×ULN; serum creatinine≤1.5×ULN;
  • For female that non-surgical sterilization or in childbearing age need to use a medically approved contraceptive (such as an intrauterine device, contraceptive or condom) during the study period and within 3 months after the end of the study treatment period; For female that non-surgical sterilization or in childbearing age must have a negative serum or urine HCG test within 72 hours prior to study enrollment; and must be nonlactating; for male patients whose partner in a childbearing age, effective methods of contraception should be given during the trial and at the end of Sintilimab injection.

Who cannot join

  • The patient has any active auto-immune disease or a history of autoimmune disease (such as the following, but not limited to: auto-immune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroid hyperfunction; patients with vitiligo. For patient with history of asthma, complete remission of asthma in childhood without any intervention after adulthood can be included, while those asthma patients who require bronchodilators for medical intervention cannot be included.);
  • The patient is using immunosuppressive agents or systemic hormonal therapy for immunosuppression purposes (dose > 10 mg/day of prednisone or other therapeutic hormones) and continues to be used within 2 weeks prior to enrollment;
  • Severe allergic reactions to other monoclonal antibodies;
  • Known for a history of central nervous system metastasis or hepatic encephalopathy;
  • Having a history of organ transplantation;
  • Patients with clinically symptomatic ascites who require puncture, drainage, or ascites drainage within 3 months, except for those who have a small amount of ascites but no clinical symptoms;
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  • Suffering from hypertension, and cannot be well controlled by antihypertensive drugs (systolic blood pressure≥140mmHg or diastolic blood pressure≥90 mmHg);
  • Suffering heart diseases with clinical symptoms or those not well controlled, such as: (1) heart failure in NYHA class 2 or higher; (2) unstable angina; (3) myocardial infarction occurred within 1 year; (4) clinically symptomatic supraventricular or ventricular arrhythmia requiring treatment or intervention; (5) Tc > 450ms (male); Tc > 470ms (female);
  • Coagulation dysfunction (INR>2.0, PT>16s), bleeding tendency or receiving thrombolysis or anticoagulant therapy, allowing prophylactic use of low-dose aspirin or low molecular heparin;
  • There are significant clinically significant bleeding symptoms or clear bleeding tendency within 3 months before enrollment, such as hemoptysis of 2.5ml or more per day, gastrointestinal bleeding, esophageal varices with bleeding risk, hemorrhagic gastric ulcer or vasculitis, etc. If the fecal occult blood is positive in the baseline period, it can be watched, then gastroscope is needed for those fecal occult blood is still positive. If the gastroscope indicates severe esophageal varices, it cannot be enrolled, except for those who have undergone gastroscopy within a month or less to exclude such cases);
  • Events of arterial/venous thrombosis occurring within the first 6 months of enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
  • There are known hereditary or acquired bleeding and thrombophilia (such as hemophilia patients, coagulopathy, thrombocytopenia, etc.);
  • Urine routine indicates that urine protein≥++ and 24-hour urine protein amount > 1.0g was confirmed;
  • The patient has active infection, unexplained fever (≥38.5°C) within 3 days before administration, or baseline white blood cell count>15×109/L;15 Patients with congenital or acquired immunodeficiency (such as HIVinfected patients);
  • HBV-DNA>2000 IU/ml (or 104 copies/ml); or HCV-RNA>103 copies/ml; or HBsAg+ and anti-HCV antibody positive patients;
  • The patient has had other malignant tumors in the past 3 years or at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ);
  • Patients with bone metastases who had received palliative radiotherapy >4% of the bone marrow area within 4 weeks prior to participation in the study;
  • Patients have previously received other anti-PD-1 antibody therapy or other immunotherapy against PD-1/PD-L1, or have received apatinib before;
  • Inoculation of a live vaccine within less than 4 weeks prior to study or possibly during the study period;
  • Pregnant or lactating women, or women of childbearing age who are unwilling to take contraceptive measures;
  • According to the investigators, the patient has other factors that may affect the results of the study or lead to the termination of the study, such as alcohol abuse, drug abuse, other serious diseases (including mental illness) requiring combined treatment, and serious laboratory tests, abnormalities, accompanied by factors such as family or society, which may affect the safety of enrolled patients.

Trial locations and contacts

5 sites in 1 country.

Yang-Kui Gu, Prof. contact

+862087345272

guyk@sysucc.org.cn

Meng-Xuan Zuo, Dr. contact

zuomx@sysucc.org.cn

5 sites in 1 country

China5 sites, 5 recruiting

  • Xiangya Hospital of Central South University

    Changsha, Hunan, 410013

    Liang-rong Shi, Prof., 13974886662 ext. 13974886662

    Not yet recruiting

  • Yang-Kui Gu

    Guangzhou, Guangdong, 510060

    Yang-Kui Gu, Prof., +862087343272 ext. 13822197618, guyk@sysucc.org.cn

    Meng-Xuan Zuo, Dr., 18924266069 ext. 18924266069, zuomx@sysucc.org.cn

    Recruiting

  • Sun Yat-Sen Memorial Hospital

    Guangzhou, Guangdong, 510120

    Zhi-yu Xiao, Prof., 13682283695 ext. 13682283695

    Not yet recruiting

  • Nanfang Hospital of Southern Medical University

    Guangzhou, Guangdong, 510510

    Jing-zhang Chen, Prof., 13802522545 ext. 13802522545

    Not yet recruiting

  • The Third Affiliated Hospital of Sun Yat-Sen University

    Guanzhou, Guangdong, 510630

    Nan Lin, Prof., 13925027138 ext. 13925027138

    Not yet recruiting

Other trials in China

About this study

Official title: A Prospective, Single-arm, Multicenter, Phase II Trial to Evaluate the Effectiveness and Safety of Hepatic Arterial Infusion Chemotherapy (HAIC) of Oxaliplatin, 5-fluorouracil and Leucovorin (mFOLFOX7) Combined With Bevacizumab and Sintilimab for Unresectable A-staged Hepatocellular Carcinoma in BCLC Classification

This study was designed to evaluate the effectiveness and safety of hepatic arterial infusion chemotherapy combined with Bevacizumab and Sintilimab (Triplet-combined Therapy) for Unresectable A-staged Hepatocellular Carcinoma in BCLC classification.

The primary outcome measure is to evaluate the objective response rate (ORR RECIST 1.1) of Triplet-combined Therapy for Unresectable A-staged Hepatocellular Carcinoma in BCLC classification.

Read more

The secondary Outcome measures include the objective response rate (ORR mRECIST 1.1), duration of response (DOR), disease control rate (DCR), progression-free survival rate (PFSR) [ Time Frame: 6- and 12-month], overall survival rate (OSR) [ Time Frame: 6- and 12-month], the median progression-free survival time (mPFS) and median overall survival time (mOS) of Triplet-combined Therapy for Unresectable A-staged Hepatocellular Carcinoma in BCLC classification.

Moreover, this study aims to assess the safety and tolerability of Triplet-combined Therapy for Unresectable A-staged Hepatocellular Carcinoma in BCLC classification.

Read the detailed description

Primary liver cancer is a common malignant tumor of the digestive system in the world. There are about 854,000 new incidences and 810,000 mortality each year. In China, there is a high incidence of liver cancer, with about 466,000 new cases and 422,000 mortality each year. Hepatocellular carcinoma (HCC) accounted for about 90% of primary liver cancer in pathological type. Most patients have reached advanced stage or are unresectable when diagnosed and the natural median survival time is only 3 to 4 months. Then only systemic therapy is recommended for patients in advanced HCC in many global guidelines. Hepatic arterial infusion chemotherapy (HAIC) of mFOLFOX7, anti-angiogenic targeting drugs, and antibody immunotherapy against programmed death molecule-1 (PD-1) immunological checkpoints are effective treatment options for advanced hepatocellular carcinoma. Many clinical studies have shown that the two-two combination of the above three treatment options can improve the anti-tumor overall response rate, the survival rate and even achieve clinical complete remission of patients with unresectable HCC. Shi Ming et al reported HAIC combined with systemic targeted therapy has a better survival outcome compared to systemic targeted therapy monotherapy [OS 13.37 vs 7.13 months, PFS 7.03 vs 2.6 months] in JAMA Oncology. In summary, for patients of unresectable Hepatocellular Carcinoma, HAIC, antiangiogenic targeted therapy, and anti-PD-1 immunotherapy have their important status, and the combination of any two treatments brings about synergy effect. Then, could the combination of the three treatment methods further improve the outcome of unresectable hepatocellular carcinoma? This study was designed to evaluate the efficacy and safety of a combination of hepatic arterial infusion chemotherapy, targeted drugs (Apatinib), and anti-PD-1 immunotherapy (Camrelizumab) to provide a more effective and toxic-tolerable treatment for patients in unresectable A-staged Hepatocellular Carcinoma in BCLC classification. This is a single-arm phase II study, and 30 patiented will be enrolled. The patients will receive Hepatic Arterial Infusion(mFOLFOX7) on the first day, and intravenous infusion of Bevacizumab on the 4th day, and intravenous infusion of Sintilimab on the 25th day. The intervention is repeated every 3 weeks. The primary outcome measure is ORR by RECIST 1.1.

Being tested
Hepatic Arterial Infusion(mFOLFOX7) combined with Bevacizumab and Sintilimab
Keywords
Unresectable Hepatocellular Carcinoma, hepatic arterial infusion chemotherapy, Bevacizumab, Sintilimab

What participants receive

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

  • Hepatic Arterial Infusion(mFOLFOX7) combined with Bevacizumab and SintilimabDrug

    The patient will receive Hepatic Arterial Infusion(mFOLFOX7) on the first day, and intravenous infusion of Bevacizumab on the 4th day, and intravenous infusion of Sintilimab on the 25th day. The intervention is repeated every 3 weeks.

Study groups in NCT05214339
Study groupRoleWhat they receive
TRIPLETExperimentalCombination Product: Hepatic Arterial Infusion combined with Bevacizumab and Sintilimab Drug: FOLFOX Protocol (Oxaliplatin, fluorouracil, and leucovorin); Bevacizumab and Sintilimab for injection. Procedure: 1. On the first day of treatment, HAIC was conducted through a catheter intubated into the tumor feeding artery under DSA guidance with the following chemotherapeutic drugs (mFOLFOX7, oxaliplatin 85 mg/m2 2 hours, folinic acid 400 mg/m2, 5-FU 2500 mg/m2 46 hours) pumped into the tumor artery. The HAIC is repeated every 3 weeks. The cumulative maximum sessions of HAIC is up to 6 times. 2. Intravenous infusion of Bevacizumab 7.5mg/kg every 3 weeks on the 4th day. 3. On the 25nd day of treatment, namely the second session of HAIC, intravenous infusion of Sintilimab 200mg every 3 weeks. 4. The cumulative maximum drug use period is up to 1 years. The patient is concurrent on medication until the treatment discontinuation criteria specified in the protocol appear.
Receives: Drug: Hepatic Arterial Infusion(mFOLFOX7) combined with Bevacizumab and Sintilimab

What is being measured

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

  1. Objective response rate (ORR) by RECIST 1.1

    ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1

    Measured: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 3 years)

Secondary outcomes (9)

  1. Objective response rate (ORR) by mRECIST

    ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by mRECIST

    Measured: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 3 years)

  2. The disease control rate (DCR)

    DCR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) or stable disease (SD) at the time of data cutoff as assessed by RECIST 1.1 and mRECIST

    Measured: From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 3 years)

  3. Duration of response (DOR) by RECIST 1.1 and mRECIST

    DOR is defined as the time from the first documentation of CR or PR to the date of first documentation of disease progression or death (whichever occurs first) as assessed by RECIST 1.1 and mRECIST

    Measured: From the first documentation of CR or PR to the first date of documentation of disease progression or death whichever occurs first (up to approximately 3 years)

  4. The progression-free survival rate (PFSR) by RECIST 1.1 and mRECIST

    Measured: From date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurs first (up to approximately 3 years)

  5. The overall survival rate (OSR)

    Measured: From date of first dose of study drug to the date of first documentation of death from any cause, whichever occurs first (up to approximately 3 years)

  6. The progression-free survival time (mPFS)

    The progression-free survival time (mPFS) defined as the time from the first study dose date to the date of first documentation of disease progression as assessed by RECIST 1.1 and mRECIST

    Measured: From date of first dose of study drug to the date of first documentation of disease progression (up to approximately 3 years)

  7. The median overall survival time (mOS)

    OS is measured from the start date of the Treatment Phase (date of first study dose) until date of death from any cause. Participants who are lost to follow-up and the participants who are alive at the date of data cutoff will be censored at the date the participant was last known alive or the cut-off date, whichever comes earlier.

    Measured: From the start date of the Treatment Phase until date of death from any cause (up to approximately 3 years)

  8. Surgical conversion rate

    Measured: From the start date of the Treatment Phase until date of Surgical resection(up to approximately 20 weeks)

  9. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Measured: From the start date of the Treatment Phase until date of death from any cause (up to approximately 3 years)

Timeline

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

  1. First posted28 Jan 2022
  2. Study start16 Mar 2022
  3. Primary completion1 Jan 2023 (estimated)
  4. Study completion1 Jun 2023 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05214339
Sponsor's protocol ID
D-TRIPLET
Status last verified
May 2022
First submitted
30 Dec 2021
Last updated
5 May 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Hepatic Arterial Infusion(mFOLFOX7) combined with Bevacizumab and Sintilimab in people with Unresectable Hepatocellular Carcinoma and Hepatocellular Carcinoma by BCLC Stage, run by Sun Yat-sen University at 5 sites 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 16 inclusion and 21 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 5 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites 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 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?

Contact Yang-Kui Gu, Prof. (+862087345272, guyk@sysucc.org.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) by RECIST 1.1 (time frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 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 NCT05214339.

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 5 May 2022.

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