AzTrials
AzTrials

Potentially Resectable Hepatocellular CarcinomaPhase 2NCT06143579

A Study of HAIC Combined With Lenvatinib and Envolizumab in Potentially Resectable Hepatocellular Carcinoma

A Phase 2 study testing FOLFOX-HAIC+Lenvatinib+Envolizumab in people with Potentially Resectable Hepatocellular Carcinoma, run by Sun Yat-sen University.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This is a single term, open label, single Center, Phase II Trial. The study is to explore the efficacy and safety of FOLFOX-HAIC combined with Lenvatinib and Envolizumab in the treatment of patients with potentially resectable HCC. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
FOLFOX-HAIC+Lenvatinib+Envolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
No sites listed yet
Study dates
15 Dec 2023to 31 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Patients who have signed ICF and are able to perform follow-up visits and relevant procedures required in the protocol;
  • Age ≥ 18 years (at the time of signing the ICF);
  • Clinically, histologically or pathologically confirmed hepatocellular carcinoma without extrahepatic metastases;
  • No previous treatment containing PD- (L) 1 inhibitor and Lenvatinib;
  • Potentially resectable HCC: (1)At least one measurable lesion (according to RECIST 1.1 criteria); (2)Patients with stage IIb/IIIa (equivalent to BCLC B/C) with portal vein tumor thrombus (according to Japanese PVTT grading criteria Vp3-Vp4) or more than three tumor nodules; (3)According to the assessment of the site multidisciplinary team (MDT), like surgical resection is not currently the treatment of choice;
  • ECOG score: 0 ~ 1;
Show all 12Show fewer
  • Child-Pugh score of ≤ 7
  • Estimated survival of more than 6 months;
  • Vital organ function meets the following requirements: (1) Blood routine: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelet count (PLT) ≥ 100 × 109/L; Hemoglobin (HGB) ≥ 90 g/L; (2) Liver function: Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN) or clearance of creatinine ≥ 50 mL/min (Cockcroft-Gault formula); Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels ≤ 2.5 × upper limit of normal (ULN); (3) Kidney function: Urine protein < 2 +; if urine protein ≥ 2 +, 24-h urine protein quantitation test result should be ≤ 1 g;
  • Normal coagulation function, no active bleeding and thrombosis (1) International normalized ratio (INR) ≤ 1.5 × ULN; (2) Active partial thromboplastin time (APTT) ≤ 1.5 × ULN; (3) Prothrombin time (PT) ≤ 1.5 × ULN;
  • Female patients of childbearing age or male patients with female sexual partners of childbearing age should take effective contraceptive measures during study treatment and for 3 months after the end of study treatment; serum or urine HCG tests must be negative and must be non-lactating within 7 days before study enrollment;
  • Patients should be compliant and cooperative with safety and survival follow-up.

Who cannot join

  • Participate in other interventional clinical studies;
  • Previous or concurrent other malignancies;
  • History of liver transplantation or undergo liver transplantation;
  • History of hypersensitivity to macromolecular protein preparations, the study drug or any of the excipients;
  • Active autoimmune disease or history of autoimmune diseases (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, previous thyroid surgery); Require bronchodilators for medical intervention of asthma; the patient has vitiligo or has complete remission of asthma in childhood, no intervention is required after adults can be included;
  • Use immunosuppressive agents, or systemic or absorbable local hormone therapy to achieve immunosuppressive purposes (dose > 10 mg/day prednisone or other effective hormones), and continue to use within 2 weeks before enrollment;
Show all 14Show fewer
  • Uncontrolled cardiac clinical symptoms or diseases, for example: (1) NYHA class 2 or higher heart failure;(2) Unstable angina pectoris; (3) Myocardial infarction within 1 year; (4) Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention;
  • Use traditional Chinese medicine immunomodulator within 2 weeks before enrollment;
  • Severe active infection or unexplained fever > 38.5 degrees during screening and before the first dose (subjects can be enrolled due to tumor-induced fever at the investigator discretion);
  • Congenital or acquired immunodeficiency: (1)HIV infection; (2)Active hepatitis (hepatitis B reference: HBV DNA ≥ 1000 IU/mL; hepatitis C reference: HCV RNA ≥ 1000 IU/mL); chronic hepatitis B virus carriers, HBV DNA < 2000 IU/ml, must receive concurrent antiviral therapy during the trial to be enrolled;
  • Live vaccines less than 4 weeks prior to study medication or likely during the study;
  • History of psychiatric drug abuse, alcoholism, or drug abuse;
  • Chinese herbal medicine within 4 weeks prior to first treatment;
  • Factors that may cause forced halfway termination of this study, such as other serious diseases (including mental illness) requiring concomitant treatment, serious laboratory abnormalities, accompanied by family or social factors, which may affect the subject' s safety, the collection of data and samples, or other circumstances which are unsuitable for subject enrollment as judged by the investigator.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Zhongguo Zhou contact

zhouzhg@sysucc.org.cn

Chaoqun Li contact

+86 20-87343879

lichq@sysucc.org.cn

About this study

Official title: FOLFOX-Hepatic Arterial Infusion Chemotherapy (HAIC) Combined With Lenvatinib and Envolizumab in Potentially Resectable Hepatocellular Carcinoma:A Single-arm, Open-label, Single Center, Phase II Trial

This is a single term, open label, single Center, Phase II Trial. The study is to explore the efficacy and safety of FOLFOX-HAIC combined with Lenvatinib and Envolizumab in the treatment of patients with potentially resectable HCC.

Read the detailed description

At present, surgery is the preferred modality for the treatment of HCC patients with radical cure and long-term survival. However, 70% to 80% of HCC is advanced, and only 15% to 30% of patients are able to undergo surgical resection. For unresectable HCC, transformation therapy is currently used, and the response rate can be effectively increased through the "TKI plus IO" or "TKI plus IO and local therapy" regimen. For locally advanced HCC (stage III-IV), HAIC or HAIC + systemic therapy is recommended. And the first-line treatment of advanced HCC, TKI (Lenvatinib, Donafenib) or IO combined TKI are recommended. For patients with potentially resectable HCC, there are currently few explorations, and more effective treatment options and evidence-based medical evidence are needed. Therefore, this study investigated the efficacy and safety of FOLFOX-HAIC combined with Lenvatinib and Envolizumab in the treatment of patients with potentially resectable HCC, and explored the relationship between biomarkers, prognostic factors and efficacy.

Being tested
FOLFOX-HAIC+Lenvatinib+Envolizumab
Keywords
HAIC, Lenvatinib, Envolizumab, PD-L1, TKI, potentially resectable HCC

What participants receive

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

  • FOLFOX-HAIC+Lenvatinib+EnvolizumabDrug

    Also called KN035

    FOLFOX-HAIC: Oxaliplatin 130 or 85 mg/m2; leucovorin 200 mg/m2; fluorouracil 400 mg/m2 intravenous bolus followed by fluorouracil 2400 mg/m2 continuous infusion over 23 hours, Q3W, 2 to 4 cycles;

    Lenvatinib: 8 mg/day (BW < 60 kg) or 12 mg/day (BW ≥ 60 kg), PO, 3-4 cycles;

    Envolizumab: 300 mg, SC, Q3W, 3-4 cycles.

Study groups in NCT06143579
Study groupRoleWhat they receive
TreatmentExperimentalFOLFOX-HAIC + Lenvatinib + Envolizumab
Receives: Drug: FOLFOX-HAIC+Lenvatinib+Envolizumab

What is being measured

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

  1. AEs

    Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0

    Measured: Up to 60 days after last treatment or 30 days after surgery

  2. Overall response rate (ORR)

    Defined as proportion of patients who have a best response of CR or PR

    Measured: At the end of Cycle 4 (each cycle is 21 days)

Secondary outcomes (6)

  1. Pathological complete response (pCR)

    According to post-operative pathology, the proportion of tumor necrosis, viable. tumor cells, and tumor infiltrating lymphocytes indicated by surgical resected specimens.

    Measured: At the end of the surgery

  2. Major Pathological Response(MPR)

    Survival tumor ≤10% after surgery

    Measured: At the end of the surgery

  3. R0 resection rate

    The tumor was completely removed during surgery, and the resection margin was negative when observed microscopically without residual components of the tumor

    Measured: At the end of the surgery

  4. 1-year recurrence-free survival(RFS) rate

    Subjects underwent radical resection from the start until the date of the first documented tumor into recurrence or death from any cause in, whichever occurred first within 1 year after surgery

    Measured: Up to one years

  5. Recurrence-free survival(RFS)

    Subjects underwent radical resection from the start until the date of the first documented tumor into recurrence or death from any cause, whichever occurred first

    Measured: Up to two years

  6. Overall survival (OS)

    Defined as the time from enrollment to death from any cause

    Measured: Up to 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 posted22 Nov 2023
  2. Study start15 Dec 2023 (estimated)
  3. Primary completion3 Mar 2025 (estimated)
  4. Study completion31 Dec 2026 (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
48 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06143579
Sponsor's protocol ID
B2023-561-01
Status last verified
Nov 2023
First submitted
16 Nov 2023
Last updated
22 Nov 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W, Li X, Wang L, Wang L, Liu Y, Liu J, Zhang M, Qi J, Yu S, Afshin A, Gakidou E, Glenn S, Krish VS, Miller-Petrie MK, Mountjoy-Venning WC, Mullany EC, Redford SB, Liu H, Naghavi M, Hay SI, Wang L, Murray CJL, Liang X. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2019 Sep 28;394(10204):1145-1158. doi: 10.1016/S0140-6736(19)30427-1. Epub 2019 Jun 24.

    PubMed 31248666

  • Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763.

    PubMed 36633525

  • Akateh C, Black SM, Conteh L, Miller ED, Noonan A, Elliott E, Pawlik TM, Tsung A, Cloyd JM. Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma. World J Gastroenterol. 2019 Jul 28;25(28):3704-3721. doi: 10.3748/wjg.v25.i28.3704.

    PubMed 31391767

  • Zhang T, Zhang L, Xu Y, Lu X, Zhao H, Yang H, Sang X. Neoadjuvant therapy and immunotherapy strategies for hepatocellular carcinoma. Am J Cancer Res. 2020 Jun 1;10(6):1658-1667. eCollection 2020.

    PubMed 32642282

  • Papadopoulos KP, Harb W, Peer CJ, Hua Q, Xu S, Lu H, Lu N, He Y, Xu T, Dong R, Gong J, Liu D. First-in-Human Phase I Study of Envafolimab, a Novel Subcutaneous Single-Domain Anti-PD-L1 Antibody, in Patients with Advanced Solid Tumors. Oncologist. 2021 Sep;26(9):e1514-e1525. doi: 10.1002/onco.13817. Epub 2021 May 27.

    PubMed 33973293

  • Chen M, Jiang M, Wang X, Shen L, Li J. Envafolimab - first PD-1/PD-L1 antibody to be administered by subcutaneous injection for microsatellite instability-high or deficient mismatch repair advanced solid tumors. Expert Opin Biol Ther. 2022 Oct;22(10):1227-1232. doi: 10.1080/14712598.2022.2125799. Epub 2022 Sep 20.

    PubMed 36124972

  • Shimizu T, Nakajima TE, Yamamoto N, Yonemori K, Koyama T, Kondo S, Sunakawa Y, Izawa N, Horie Y, Xiang S, Xu S, Qin L, Gong J, Liu D. Phase I study of envafolimab (KN035), a novel subcutaneous single-domain anti-PD-L1 monoclonal antibody, in Japanese patients with advanced solid tumors. Invest New Drugs. 2022 Oct;40(5):1021-1031. doi: 10.1007/s10637-022-01287-7. Epub 2022 Aug 6.

    PubMed 35932387

  • Huang X, Xu L, Ma T, Yin X, Huang Z, Ran Y, Ni Y, Bi X, Che X. Lenvatinib Plus Immune Checkpoint Inhibitors Improve Survival in Advanced Hepatocellular Carcinoma: A Retrospective Study. Front Oncol. 2021 Nov 16;11:751159. doi: 10.3389/fonc.2021.751159. eCollection 2021.

    PubMed 34868952

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing FOLFOX-HAIC+Lenvatinib+Envolizumab in people with Potentially Resectable Hepatocellular Carcinoma, run by Sun Yat-sen University.

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 12 inclusion and 14 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: opening soon, as of the sponsor's last update on 22 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Zhongguo Zhou (zhouzhg@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AEs (time frame: Up to 60 days after last treatment or 30 days after surgery). The study lists 2 primary outcomes in all. 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 NCT06143579, which also lists 8 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 22 Nov 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in