Trial Title:
TACE Combined With Camrelizumab and Apatinib in the Treatment of Advanced Liver Cancer
NCT ID:
NCT05550025
Condition:
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma, Hepatocellular
Liver Neoplasms
Apatinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Unknown status
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
camrelizumab& apatinib
Description:
TACE（transcatheter arterial chemoembolization） combined with Apatinib and Camrelizumab
Camrelizumab 200mg every 3 weeks. Taking Apatinib-Mesylate Tablets (250 mg/tablet) orally
after meals, once a day, for continuous medication.
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.
Arm group label:
TACE combined with Apatinib and Camrelizumab
Summary:
This study was designed to evaluate the effectiveness and safety of TACE（transcatheter
arterial chemoembolization） combined with Apatinib and Camrelizumab for Hepatocellular
Carcinoma.
The primary outcome measure is to evaluate the objective response rate (ORR) of the
therapy for Hepatocellular Carcinoma.
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 the therapy for Hepatocellular
Carcinoma.
Moreover, this study aims to assess the safety and tolerability of the Therapy for
Hepatocellular Carcinoma.
Detailed description:
Hepatocellular carcinoma is a common high-grade malignant tumor in my country, with
limited treatment options and poor prognosis. Transcatheter arterial chemoembolization
(TACE) is currently recognized as an effective method for the treatment of unresectable
hepatocellular carcinoma. Intra-arterial administration and embolization are the two
major features of TACE treatment techniques. However, conventional TACE (conventional
TACE, CTACE) mainly focuses on the efficacy of embolization, and the effect of
chemotherapy is not ideal. The emergence of drug-eluting beads (DEB) enhances the effect
of chemotherapy in TACE, which is of great significance to improve the overall efficacy
of TACE in hepatocellular carcinoma. However, the long-term efficacy of TACE in the
treatment of liver cancer is not very satisfactory. Changes in the tumor microenvironment
after TACE can induce abnormally elevated expression of tumor progression-related
factors, which makes liver cancer cells prone to local recurrence and distant metastasis,
which seriously affects the prognosis of liver cancer patients. Clinical studies have
shown that the complete tumor necrosis rate of TACE treatment of liver cancer is only
10-20%, and the median survival time of patients is only 16-20 months. Therefore, the
poor long-term efficacy of TACE is an urgent bottleneck for its application in the
clinical treatment of liver cancer.
With the deepening of tumor immune theory research, based on overcoming the immune escape
of swelling and pain, the therapy that produces a specific and efficient immune response
to swelling and pain has gradually become a hot spot in tumor research, and great
progress has been made. Tumor immunotherapy has the advantages of high specificity,
remarkable curative effect, and slight damage to normal organisms.The 2018 Nobel Prize in
Physiology or Medicine was awarded to American scientist James R Alison and Japanese
scientist Tasuku Honjo for their pioneering contributions to tumor immunotherapy. With
the in-depth study of the theory of swelling and pain immunology and the continuous
progress of treatment technology, it is expected to achieve a new breakthrough in the
radical cure of swelling and pain, and has gradually become the mainstream method of
tumor treatment.
Programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling pathway is
currently the most mature and fastest-growing tumor immunotherapy molecule target. PD-1
plays a role in the effector phase of the immune response and is expressed on activated T
cells, B cells and myeloid cells. PD-1 has two ligands, namely PD-L1 and PD-L2. Both
PD-L1/L2 are expressed in antigen-presenting cells, and PD-L1 is also expressed in
various tumor tissues. The combination of PD-1 and PD-L1 mediates the co-inhibitory
signal of T cell activation, inhibits the killing function of T cells, and negatively
regulates the human immune response. Therefore, immunomodulation targeting PD-1/PD-L1 is
of great significance for anti-tumor therapy.
Camrelizumab is a humanized PD-1 monoclonal antibody independently developed by Jiangsu
Hengrui Medicine. It has completed a phase clinical study for the treatment of solid
pain. The results show that camrelizumab has the potential to treat advanced solid pain.
Good safety and tolerability. Objective response rate of camrelizumab in patients with
previously treated advanced hepatocellular carcinoma. A multi-center clinical trial of
patients who received at least TACE. Combination with camrelizumab and apatinib in the
treatment of advanced liver tumors. A single-center, pre-fragile, single-arm, phase I
clinical study Among patients receiving first-line systemic therapy, the 6-month overall
survival rate was 74.4% (95%CI.68.0-79.7), with anti-swelling and pain activity, and the
safety was controllable, so camrelizumab was approved for liver cancer indications on
March 6, 2020 , for patients with advanced hepatocellular carcinoma who have previously
received sorafenib and/or oxaliplatin-containing 14.7%(95%CI 10.3-20.2), systemic
chemotherapy.
Apatinib is a new-generation small-molecule vascular endothelial growth factor receptor-2
(VEGFR-2) tyrosine kinase inhibitor, and the world's first small-molecule anti-angiogenic
target proven safe and effective in the treatment of advanced gastric cancer Xiang drug,
independently developed by Jiangsu Hengrui Medicine, its main mechanism of action is to
highly selectively inhibit the signal transduction of VEGFR-2 combined with the
micro-activity of succinic acid, yang-blocking vascular endothelial growth factor (VEGF),
thereby effectively inhibiting the Swelling angiogenesis. In 2020, the "randomized,
bilingual, placebo-controlled phase W AHELP study of second-line apalachone in the
treatment of late Ming hepatocellular brain (CHCC)" jointly conducted by 31 tumor centers
across the country" was accepted by the ASCO General Assembly and selected as an oral
presentation. The results of the study showed that, compared with placebo, apatinib
significantly prolonged median OS in previously treated Chinese patients with advanced
HCC (8.7 months vs 6.8 months). In addition, the median progression-free survival (PFS)
in the apatinib group was 4.5 months, compared with 19 months in the placebo group. at
the same time, the objective response rate (ORR) of the apatinib group was 10.7%, which
was significantly higher than that of the control group of 1.5%. In terms of safety,
treatment-related adverse events were similar to those already approved for the treatment
of late-stage gastric cancer, no new adverse events were observed, and patients were well
tolerated. Although apatinib has been submitted to the CFDA for second-line indications
for hepatocellular carcinoma, it has not yet been officially approved, so it has not been
written in the instructions, that is, it is an off-label drug.
A phased study of apalacone combined with transarterial chemoembolization (TACE) in the
treatment of advanced liver cancer was published in the journal Cancer Biology & Therapy.
Preliminary conclusions showed that apazatinib combined with TACE treatment significantly
improved ORR at 9 and 12 months, and the median PFS was also significantly better than
the control group (12.5 months vs. .6.0 months). Another single-center retrospective
study also confirmed that, the PFS and OS of apalacone combined with TACE in the
treatment of advanced liver tumors were significantly better than those of the control
group. It can be seen that combined with apatinib treatment on the basis of TACE,
hopefully better Inhibit the growth of swelling disease to prolong the disease-free
survival period and improve the survival rate of patients. In 2018, a retrospective study
was published at the World Congress on Pain and Pain Intervention (WCIO), suggesting the
survival benefit of apalacone combined with TACE in the treatment of patients with HCC
and portal vein tumor thrombus (PVTT). Apatinib combined with camrelizumab in the
treatment of advanced liver cancer, gastric cancer and esophagogastric junction cancer!
The phase clinical study also showed the synergistic effect of immunotherapy and
anti-angiogenic therapy, of which 16 cases of liver cancer can be evaluated for efficacy,
ORR and DCR were 50% and 93.8%, respectively. The results of the study were presented at
the ASCO. Annual meeting. Apatinib in combination with camrelizumab for advanced liver
cancer due to encouraging findings Phase clinical research is also actively carried out,
and all subjects have now been enrolled. At the same time, a single-center study on the
efficacy and safety of apatinib combined with camrelizumab versus sorafenib in the
first-line treatment of advanced hepatocyte TACE combined with camrelizumab and apatinib
in the treatment of advanced liver cancer , Prospective, single-arm, Phase II clinical
trials of cancer cells in Sichuan have also been launched simultaneously in China, the
United States, and Europe. This randomized, controlled, open-label, international
multi-center study is the first exploration of the combination of PD-1 monoclonal
antibody and anti-vascular targeting in my country in the field of liver cancer in the
world. We look forward to the announcement of the follow-up research results.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years old, ≤ 70 years old, both men and women;
2. Clinical or pathologically confirmed BCLC C-stage hepatocellular carcinoma, no
further first-line treatment;
3. At least one intrahepatic evaluable tumor existed, intrahepatic tumor is the primary
tumor burden;
4. Child-Pugh score small or equal to 7 points (Child-Pugh A-B);
5. The liver tumor burden does not exceed 50% of the total liver volume;
6. Patient can swallow tablet normally;
7. ECOG score: 0 to 1 (according to the ECOG score classification);
8. The expected survival is longer than 12 weeks;
Exclusion Criteria:
1. 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.);
2. 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;
3. Severe allergic reactions to other monoclonal antibodies;
4. Known for a history of central nervous system metastasis or hepatic encephalopathy;
5. Having a history of organ transplantation;
6. 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;
7. Suffering from hypertension, and cannot be well controlled by antihypertensive drugs
(systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥90 mmHg);
8. 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);
9. 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;
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Address:
City:
Guangzhou
Zip:
510000
Country:
China
Status:
Recruiting
Contact:
Last name:
xu linfeng
Phone:
13826263989
Email:
xulf1@21cn.com
Contact backup:
Last name:
ni jiayan
Phone:
13660140273
Email:
jiayan0129@126.com
Start date:
December 17, 2021
Completion date:
February 11, 2024
Lead sponsor:
Agency:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Agency class:
Other
Collaborator:
Agency:
Jiangsu Hengrui Pharmaceutical Co., Ltd.
Agency class:
Industry
Source:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05550025
