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Hepatocellular CarcinomaPhase 1/2NCT04443309

Lenvatinib in Combination With Camrelizumab as First-Line Therapy in Patients With Advanced HCC

A Phase 1/2 study testing Camrelizumab and Lenvatinib in people with Hepatocellular Carcinoma, run by Peking Union Medical College Hospital 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 The sponsor has not verified this record for over two years, so it may be out of date.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 is a single arm, open-label, non-randomized and single-center phase I/II clinical study, to evaluate the the safety, tolerance and efficacy of Lenvatinib plus Camrelizumab as first-line therapy in patients with advanced Hepatocellular Carcinoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
Camrelizumab and Lenvatinib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
1 siteChina
Study dates
11 Sep 2020to Aug 2024
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol;
  • Males or females, age ≥ 18 years at the time of informed consent;
  • Imaging (by AASLD or Standard for the diagnosis and treatment of primary liver cancer 2017 in China) or histopathologically or cytologically confirmed advanced HCC;
  • BCLC stage B or C, and not suitable for surgical or local therapy, or has progressed following surgical and/or local therapy;
  • No previous systematic treatment for HCC;
  • Have at least one measurable lesion (in accordance with RECIST v1.1); the measurable lesion has a long diameter ≥ 10 mm or lymphadenopathy has a short diameter ≥ 15 mm in spiral CT scan;
Show all 13Show fewer
  • ECOG-PS score 0 or 1
  • Child-Pugh Class: Grade A
  • Life Expectancy of at least 3 months
  • Subjects with HBV infection: HBV DNA<2000 IU/ml or <10^4 copy/mL, and have received anti-HBV therapy for at least 14 days prior to enrollment in the study, subjects with HCV-RNA(+) must receive antiviral therapy;
  • Hematology and organ functions are sufficient based on the following laboratory results within 14 days prior to the treatment of this study:
  • Whole blood cell examination (no blood transfusion within 14 days, no G-CSF use and no drugs use): WBC ≥ 3.0×10^9/L, HB ≥ 85 g/L; Neutrophils ≥ 1.5×10^9/L; PLT≥75×10^9/L; Biochemical examination (no ALB infused within 14 days): ALB ≥ 29 g/L; ALP and ALT and AST < 5×ULN; TBIL≤3×ULN; Adequate renal function: Cr≤1.5×ULN, or CCr>50mL/min; Female: CrCl = ((140- year) x weight (kg) x 0.85)/72x Cr (mg/dL) Male: CrCl = ((140- year) x weight (kg) x 1.00)/72xCr (mg/dL)
  • Agree to abstain from sex (avoid heterosexual intercourse) or use contraceptive methods with an annual contraceptive failure rate of less than 1% during treatment and for at least 6 months after the last administration.

Who cannot join

  • Hepatocellular carcinoma patients with any of the following:
  • Suitable for radical surgery; without an assessment lesion after radical surgery; liver transplantation history or ready for liver transplantation;
  • History of hepatic encephalopathy;
  • Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and lamellar cell carcinoma;
  • Pregnant women (positive pregnancy test before taking medicine) or lactating women;
  • Known history of serious allergy to any monoclonal antibody or targeted anti-angiogenic drug (or any excipient);
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  • Received any topical treatment within 4 weeks prior to the study, including but not limited to surgery, radiotherapy, hepatic artery embolization, TACE, hepatic artery perfusion, radiofrequency ablation, cryoablation or percutaneous ethanol injection;
  • Previous or existing CTCAE 5.0 standard grade 3 or above gastrointestinal fistula or non-gastrointestinal fistula (such as skin);
  • Factors to affect oral administration and absorption (such as inability to swallow, chronic diarrhea and intestinal obstruction);
  • Ascites with clinical symptoms (i.e. ascites with Child-Pugh rating > 2) or cancerous ascites require therapeutic abdominal puncture or drainage. Or uncontrolled malignant ascites (ascites that researchers believe diuretics or puncture cannot control);
  • Major surgical operations (except biopsy) were performed within 4 weeks prior to the first study of drug therapy or the surgical incision was not completely healed; Minor surgery (i.e. simple resection, biopsy, etc.) was performed within 7 days before the first round of research intervention.
  • Cardiovascular and cerebrovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina pectoris, cerebrovascular accident or transient ischemic attack, congestive heart failure occurred within 6 months prior to admission (New York Heart Association Grade ≥2, see Appendix 4); Arrhythmia requiring antiarrhythmic drugs (except β receptor blocker or digoxin); Repeated ECG detection QTcF interval>480 milliseconds (ms).
  • Hepatic and renal insufficiency, such as jaundice, ascites, and/or bilirubin>3×ULN, creatinine ratio>3.5g/24h, or renal failure requiring blood or peritoneal dialysis, etc. And/or urine routine showed proteinuria ≥++or confirmed 24-hour proteinuria>1.0g.
  • Persistent>2 grade (CTC-AE5.0) infection.
  • History of thromboembolism (including stroke and/or transient ischemic attack) in the past 6 months.
  • Hypertension (systolic blood pressure>160mmHg, diastolic blood pressure>100 mmHg) that not be well controlled through antihypertensive drug treatment.
  • History of active autoimmune diseases or autoimmune diseases in the past two years.
  • Known central nervous system metastasis and/or cancerous meningitis.
  • Be ready for or previously received organ or allogenic bone marrow transplantation.
  • Known history of active tuberculosis (Mycobacterium tuberculosis).
  • History of gastrointestinal hemorrhage within 6 months prior to the start of study treatment or clear tendency of gastrointestinal hemorrhage.
  • History of human immunodeficiency virus (HIV)infection.
  • Active hepatitis B virus or C virus infection and not receive regular treatment;
  • Serious non-healing wound, ulcer or fracture.
  • Drug abuse exists; or any medical, psychological or social condition that may affect research, unstable patient compliance or even endanger patient safety.
  • Any>1 grade (CTC-AE 5.0) unresolved toxicity due to previous treatment or operation, except for hair loss, anemia, and hypothyroidism.
  • Previous and current evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonia and severe impairment of lung function.
  • Received a potent CYP3A4 inhibitor treatment within 7 days prior to the study or received a potent CYP3A4 inducer within 12 days prior to the study.
  • With other active malignant tumors except HCC within 5 years or simultaneously.
  • Patients are unsuitable for participation in this research after comprehensive assessment by the researchers.
  • Patients participate in another clinical study at the same time.

Trial locations and contacts

1 site in 1 country.

Xiaobo Yang contact

010-69156043

yangxulcyx@163.com

Xiao-Bo Yang contact

010-69156043

yangxiaobo67@pumch.cn

China1 site, 1 recruiting

  • Chinese Academy of Medical Sciences & Peking Union Medical College Hospital

    Beijing, Please Select, 100730

    Xiaobo Yang, MD, 010-69156043 ext. 010-69156043, yangxulcyx@163.com

    Haitao Zhao, MD

    Recruiting

Other trials in China

About this study

Official title: A Single-arm, Non-randomized, Single-center Study to Evaluate Lenvatinib in Combination With Camrelizumab as First-Line Therapy in Patients With Advanced Hepatocellular Carcinoma

This is a single arm, open-label, non-randomized and single-center phase I/II clinical study, to evaluate the the safety, tolerance and efficacy of Lenvatinib plus Camrelizumab as first-line therapy in patients with advanced Hepatocellular Carcinoma.

Read the detailed description

The purpose of this study is to evaluate the safety, tolerance and efficacy of Lenvatinib combined with Camrelizumab as first-line therapy for patients with advanced hepatocellular carcinoma.The target sample size is 53.In the first phase 6 panticipants was evaluated (N=3+3), If there was no obvious dose-limiting toxicity (DLT), then entered the extended phase (N=47).Treatment continually until disease progression or intolerable toxicity or patients withdrawal of consent.

Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • CamrelizumabDrug

    Also called SHR-1210

    Camrelizumab 200mg,iv,d1,q2w

  • LenvatinibDrug

    Also called LENVIMA,E7080

    Lenvatinib 8mg (<60kg) or 12mg (≥60kg),po,d2,qd

Study groups in NCT04443309
Study groupRoleWhat they receive
Lenvatinib plus CamrelizumabExperimentalCamrelizumab (Jiangsu HengRui Medicine Co., Ltd.) is a recombinant anti-human PD-1 IgG4 monoclonal antibody. Lenvatinib is a novel angiogenesis inhibitor which targets multiple tyrosine kinases， including vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β, RET and KIT.
Receives: Drug: Camrelizumab; Drug: Lenvatinib

What is being measured

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

  1. Objective Response Rate (ORR)

    Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients

    Measured: one year

Secondary outcomes (8)

  1. Disease Control Rate (DCR)

    Proportion of patients whose tumor volume control (reduced or enlarged) reaches a predetermined value and can maintain a minimum time limit

    Measured: one year

  2. Progression-free Survival (PFS)

    A duration from the date of initial treatment to disease progression (defined by RECIST 1.1) or death of any cause

    Measured: one year

  3. Overall Survival (OS)

    Duration from the date of initial treatment to the date of death due to any cause.

    Measured: one year

  4. Duration of Response (DOR)

    Duration from the first time reported partial response or complete response to the first time of disease progression or death

    Measured: one year

  5. Clinical Benefit Rate (CBR)

    Proportion of patients achieved complete response and partial response for more than 6 months

    Measured: two years

  6. 3-months and 6-months Progression Free Survival Rate

    Portion of patients who do not experience disease progression (defined by RECIST 1.1) or death of any cause after treated with toripalimab plus lenvatinib for 3 months and 6 months

    Measured: 6 months

  7. 6-months and 1-year Mortality Rate

    Portion of patients who die of any cause after treated with toripalimab plus lenvatinib at 6 months and 1 year, respectively

    Measured: one year

  8. Adverse Events (AE)

    Any adverse events related with treatment drugs and details include adverse events type, frequency and severity

    Measured: two years

Timeline

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

  1. First posted23 Jun 2020
  2. Study start11 Sep 2020
  3. Primary completionAug 2024 (estimated)
  4. Study completionAug 2024 (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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
53 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04443309
Sponsor's protocol ID
JS-2286
Status last verified
Jan 2023
First submitted
21 Jun 2020
Last updated
29 Mar 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Villanueva A. Hepatocellular Carcinoma. N Engl J Med. 2019 Apr 11;380(15):1450-1462. doi: 10.1056/NEJMra1713263. No abstract available.

    PubMed 30970190

  • Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9.

    PubMed 25220842

  • Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012 Mar 31;379(9822):1245-55. doi: 10.1016/S0140-6736(11)61347-0. Epub 2012 Feb 20.

    PubMed 22353262

  • Llovet JM, Montal R, Villanueva A. Randomized trials and endpoints in advanced HCC: Role of PFS as a surrogate of survival. J Hepatol. 2019 Jun;70(6):1262-1277. doi: 10.1016/j.jhep.2019.01.028. Epub 2019 Mar 31.

    PubMed 30943423

  • Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.

    PubMed 18650514

  • Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jan;10(1):25-34. doi: 10.1016/S1470-2045(08)70285-7. Epub 2008 Dec 16.

    PubMed 19095497

  • Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.

    PubMed 29433850

  • 8. Qin S OX, Bai Y, Cheng Y, Chen Z, Ren Z, Song T, Dutcus C, Saito K, Tamai T, Yau TCC, Rau K-M, Cheng A-L, Han G. Subgroup analysis of Chinese patients in a phase 3 study of lenvatinib vs sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma. Hepatol Int 2019;13:S170.

  • Boussiotis VA. Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway. N Engl J Med. 2016 Nov 3;375(18):1767-1778. doi: 10.1056/NEJMra1514296. No abstract available.

    PubMed 27806234

  • Ma W, Gilligan BM, Yuan J, Li T. Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy. J Hematol Oncol. 2016 May 27;9(1):47. doi: 10.1186/s13045-016-0277-y.

    PubMed 27234522

  • Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.

    PubMed 32402160

  • Qin S, Ren Z, Meng Z, Chen Z, Chai X, Xiong J, Bai Y, Yang L, Zhu H, Fang W, Lin X, Chen X, Li E, Wang L, Chen C, Zou J. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol. 2020 Apr;21(4):571-580. doi: 10.1016/S1470-2045(20)30011-5. Epub 2020 Feb 26.

    PubMed 32112738

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Camrelizumab and Lenvatinib in people with Hepatocellular Carcinoma, run by Peking Union Medical College 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 13 inclusion and 31 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 29 Mar 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 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 Xiaobo Yang (010-69156043, yangxulcyx@163.com), 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: one year). 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 NCT04443309, which also lists 12 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 29 Mar 2023.

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