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C-staged Hepatocellular Carcinoma in BCLC ClassificationPhase 2TRIPLETNCT04191889

A Trial of Hepatic Arterial Infusion Combined With Apatinib and Camrelizumab for C-staged Hepatocellular Carcinoma in BCLC Classification

A Phase 2 study testing Hepatic Arterial Infusion combined with Apatinib and Camrelizumab in people with C-staged Hepatocellular Carcinoma in BCLC Classification, run by Sun Yat-sen University at 1 site 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 The sponsor has not verified this record for over two years, so it may be out of date.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
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Trial summary

This study was designed to evaluate the effectiveness and safety of hepatic arterial infusion chemotherapy combined with Apatinib and Camrelizumab (Triplet-combined Therapy) for C-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 combined with Apatinib and Camrelizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
1 siteChina
Study dates
13 Apr 2020to 31 Dec 2025
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 BCLC C-stage hepatocellular carcinoma, no further first-line treatment;
  • At least one intrahepatic evaluable tumor existed, intrahepatic tumor is the primary tumor burden;
  • Child-Pugh score small or equal to 7 points (Child-Pugh A-B);
  • The liver tumor burden does not exceed 50% of the total liver volume;
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  • Patient can swallow tablet normally;
  • ECOG score: 0 to 1 (according to the ECOG score classification);
  • The expected survival is longer than 12 weeks;
  • 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 non-lactating; for male patients whose partner in a childbearing age, effective methods of contraception should be given during the trial and at the end of Camrelizumab injection.

Who cannot join

  • The patient has any active auto-immune disease or a history of auto-immune 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); QTc > 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 HIV-infected patients);
  • 16. HBV-DNA>2000 IU/ml (or 104 copies/ml); or HCV-RNA>103 copies/ml; or HBsAg+ and anti-HCV antibody positive patients; 17. 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); 18. Patients with bone metastases who had received palliative radiotherapy >4% of the bone marrow area within 4 weeks prior to participation in the study; 19. Patients have previously received other anti-PD-1 antibody therapy or other immunotherapy against PD-1/PD-L1, or have received apatinib before; 20. Inoculation of a live vaccine within less than 4 weeks prior to study or possibly during the study period; 21. Pregnant or lactating women, or women of childbearing age who are unwilling to take contraceptive measures; 22. 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

1 site in 1 country.

Yang-kui Gu, Prof. contact

13822197618 ext. 13822197618

guyk@sysucc.org.cn

Tian-qi Zhang, Dr. contact

18620877505 ext. 18620877505

zhangtq@sysucc.org.cn

China1 site, 1 recruiting

  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510060

    Yang-kui Gu, Prof., 13822197618 ext. 13822197618, guyk@sysucc.org.cn

    Recruiting

Other trials in China

About this study

Official title: A Prospective, Single-arm, Phase II Trial to Evaluate the Effectiveness and Safety of Hepatic Arterial Infusion Chemotherapy (HAIC) of Oxaliplatin, 5-fluorouracil and Leucovorin (mFOLFOX7) Combined With Apatinib-Mesylate Tablets and Camrelizumab for Injection for C-staged Hepatocellular Carcinoma in BCLC Classification.

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

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

Read more

The secondary Outcome measures include the 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 C-staged Hepatocellular Carcinoma in BCLC classification.

Moreover, this study aims to assess the safety and tolerability of Triplet-combined Therapy for C-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 with distant metastasis 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 advanced HCC.

Shi Ming et al reported HAIC combined with systemic targeted therapy has a better survival outcome compared to systemic targeted therapy mono-therapy [OS 13.37 vs 7.13 months, PFS 7.03 vs 2.6 months] in JAMA Oncology. Although the toxicity of combination therapy is slightly higher than that of sorafenib monotherapy, these adverse effects are tolerable.

In addition, in a phase Ib study of Camrelizumab combined with apatinib in the treatment of advanced liver cancer, gastric cancer or gastroesophageal junction cancer showed that in 16 patients with HCC, the ORR was 50.0% and the DCR was 93.8%. When the dose of apatinib was 250 mg, the median PFS was 7.2 months. Camrelizumab combined with low dose apatinib can effectively reduce the incidence of adverse reactions, ≥10% of patients have treatment-related adverse reactions (all levels), no treatment-related adverse reactions leading to death. Therefore, low-dose anti-angiogenic drugs can inhibit tumor angiogenesis on the one hand, reduce immunosuppression by inducing normalization of blood vessels, enhance effector immune cell infiltration, and enhance anti-tumor immunity.

In summary, for patients of C-staged Hepatocellular Carcinoma, HAIC, anti-angiogenic 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 advanced 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 C-staged Hepatocellular Carcinoma in BCLC classification.

Being tested
Hepatic Arterial Infusion combined with Apatinib and Camrelizumab
Keywords
Advanced hepatocellular carcinoma, hepatic arterial infusion chemotherapy, anti-PD-1 immunotherapy, Camrelizumab, anti-angiogenic targeted therapy, Apatinib

What participants receive

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

  • Hepatic Arterial Infusion combined with Apatinib and CamrelizumabCombination product

    Drug: FOLFOX Protocol (Oxaliplatin, fluorouracil, and leucovorin); Camrelizumab for injection and Apatinib-Mesylate Tablets

    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. Taking Apatinib-Mesylate Tablets (250 mg/tablet) orally on day 8 in the first HAIC cycle, once a day, for continuous medication.
    3. The first dose of Camrelizumab was administered on day 4 of the second HAIC cycle, at a dose of 200 mg intravenously, every three weeks.
    4. The cumulative maximum drug use period is up to 2 years. The patient is concurrent on medication until the treatment discontinuation criteria specified in the protocol appear.
Study groups in NCT04191889
Study groupRoleWhat they receive
TRIPLETExperimentalHepatic Arterial Infusion combined with Apatinib and Camrelizumab
Receives: Combination Product: Hepatic Arterial Infusion combined with Apatinib and Camrelizumab

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 (up to approximately 3 years)

Secondary outcomes (11)

  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 (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 (up to approximately 3 years)

  3. The time to response (TTR)

    TTR was calculated as the time from treatment initiation to first documented response as assessed by RECIST 1.1 and mRECIST.

    Measured: From date of first dose of study drug to the date of first documentation of CR or PR (up to approximately 3 years)

  4. 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 as assessed by RECIST 1.1 and mRECIST or death (whichever occurs first).

    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)

  5. The progression-free survival time (PFS)

    The progression-free survival time (PFS) 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 or death, whichever comes earlier.

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

  6. The liver-specific progression-free survival time (liver-specific PFS)

    The liver-specific PFS was defined as the time from treatment initiation to disease progression within the liver as assessed by RECIST 1.1 and mRECIST or death, whichever comes earlier.

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

  7. The median overall survival time (OS)

    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.

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

  8. 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)

  9. The overall survival rate (OSR)

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

  10. 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)

  11. Exploratory outcome measure: The quality of life (QoL)

    The exploratory endpoint was the QoL, which was assessed using the European Organisation for Research and Treatment of Cancer QoL questionnaire (EORTC QLQ-C30).

    Measured: From date of first dose of study drug to the date of first documentation of disease progression within the liver or death (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 posted10 Dec 2019
  2. Study start13 Apr 2020
  3. Primary completion31 Dec 2023 (estimated)
  4. Study completion31 Dec 2025 (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
47 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04191889
Sponsor's protocol ID
TRIPLET
Acronym
TRIPLET
Status last verified
Sep 2023
First submitted
3 Dec 2019
Last updated
13 Sep 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Lyu N, Kong Y, Mu L, Lin Y, Li J, Liu Y, Zhang Z, Zheng L, Deng H, Li S, Xie Q, Guo R, Shi M, Xu L, Cai X, Wu P, Zhao M. Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma. J Hepatol. 2018 Jul;69(1):60-69. doi: 10.1016/j.jhep.2018.02.008. Epub 2018 Feb 20.

    PubMed 29471013

  • He M, Li Q, Zou R, Shen J, Fang W, Tan G, Zhou Y, Wu X, Xu L, Wei W, Le Y, Zhou Z, Zhao M, Guo Y, Guo R, Chen M, Shi M. Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion: A Randomized Clinical Trial. JAMA Oncol. 2019 Jul 1;5(7):953-960. doi: 10.1001/jamaoncol.2019.0250.

    PubMed 31070690

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Hepatic Arterial Infusion combined with Apatinib and Camrelizumab in people with C-staged Hepatocellular Carcinoma in BCLC Classification, run by Sun Yat-sen University 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 19 inclusion and 15 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 13 Sep 2023. 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 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. (13822197618 ext. 13822197618, 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 (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 NCT04191889, which also lists 2 linked publications.

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 13 Sep 2023.

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