Nocardia Rubra Cell Wall Skeleton (N-CWS) Plus HAIC, Lenvatinib and Tislelizumab in Treating Patients With Advanced HCC

NCT05533892 | Unknown Phase 1 DMC

• 1 other identifier: 2022-S038
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of Nocardia rubra cell wall skeleton plus hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin, lenvatinib and tislelizumab in patients with advanced hepatocellular carcinoma (HCC).

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) at 6 months

  ORR, as determined based on tumor response according to mRECIST, is defined as the proportion of all randomized subjects whose best overall response (BOR) is either a CR or PR.

  6 months

Secondary Outcomes (4)

• Overall survival

  6 months

• Adverse events

  6 months

• Progression free survival rate at 6 months

  6 months

• Duration of response (DOR)

  6 months

Study Arms (1)

Nocardia rubra cell wall skeleton (N-CWS) Plus HAIC, Lenvatinib and Tislelizumab

EXPERIMENTAL

N-CWS 400μg hypodermic injected every week (Q1W) for 4 weeks, following by N-CWS 400μg hypodermic injected Q4W. Hepatic arterial infusion of oxaliplatin , fluorouracil, and leucovorin every 3 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Tislelizumab 200mg intravenously every 3 weeks.

Drug: Nocardia rubra cell wall skeleton; Procedure: Hepatic arterial infusion chemotherapy; Drug: Lenvatinib; Drug: Tislelizumab

Interventions

Nocardia rubra cell wall skeleton DRUG

Nocardia rubra cell wall skeleton (N-CWS) 400μg hypodermic injected every 1 week (Q1W) for 4 weeks, following by N-CWS 400μg hypodermic injected every 4 weeks (Q4W)

Also known as: N-CWS

Nocardia rubra cell wall skeleton (N-CWS) Plus HAIC, Lenvatinib and Tislelizumab

Hepatic arterial infusion chemotherapy PROCEDURE

administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 3 weeks

Also known as: HAIC

Nocardia rubra cell wall skeleton (N-CWS) Plus HAIC, Lenvatinib and Tislelizumab

Lenvatinib DRUG

12 mg (or 8 mg) once daily (QD) oral dosing

Also known as: JieLiEn

Nocardia rubra cell wall skeleton (N-CWS) Plus HAIC, Lenvatinib and Tislelizumab

Tislelizumab DRUG

200mg intravenously every 3 weeks

Also known as: BaiZeAn

Nocardia rubra cell wall skeleton (N-CWS) Plus HAIC, Lenvatinib and Tislelizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects volunteer to participate in the study and agree to sign the informed consent with good compliance and follow-up.
• Subjects are 18 years old or older when signing the informed consent and gender is not limited.
• Subjects were diagnosed with advanced hepatobiliary malignant tumors (clinical stage IV) by imaging and histological examination, including hepatocellular carcinoma, cholangiocarcinoma, ampullary carcinoma, gallbladder carcinoma and mixed carcinoma.
• The disease is not suitable for radical surgery and/or topical treatment, or disease progression occurs after surgery and/or local treatment.
• At least one measurable lesion (according to mRECIST): the measurable lesion has a long diameter ≥ 10 mm or lymphadenpathy has a short diameter ≥ 15 mm in spiral CT scan.
• Patients fail after at least one systemic failure, including surgery, intervention, radiotherapy, chemotherapy and targeted therapy and require palliative treatment.
• Definition of treatment failure: Disease progression during treatment or relapse after treatment, such as after at least once radical or palliative resection surgery, revenue recurrence or progression after intervention therapy or radiotherapy. Intervention therapy or oxaliplatin treatment must be more than 1 cycle, and molecular targeted therapy must more than ≥14 days.
• Definition of intolerance: Grade ≥IV hematologic toxicity, or grade ≥III non- hematologic toxicity, or grade ≥ II damage of heart, liver and kidney during treatment.
• The ECOG score is 0-2 within 1 week before enrollment.
• Liver function assessment: Child-Pugh Grade A or mild Grade B (≤ 7 points), BCLC stage B-C.
• More than 2 weeks from first-line system treatment failure to sign informed consent for this study, and adverse events returned to normal (NCI-CTCAE ≤ I).
• Estimated survival time ≥ 6 months.
• HBV DNA \<2000 IU/ml (104 copies/ml).
• Hematology and organ function 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): Hb≥90g/L, ANC≥1.5×10\*9/L, PLT≥80×10\*9/L.

You may not qualify if:

• Clinical stage I-III, and/or with any of the following:
• Suitable for radical surgery,
• Or, without an assessment lesion after radical surgery,
• Or, never receive any first line treatment,
• Or, liver transplantation history or ready for liver transplantation.
• ECOG score ≥ 3 points.
• 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.
• Ascites with clinical symptoms which requires abdominal puncture or drainage therapy, or Child-Pugh score \>2.
• With serious systemic diseases such as heart disease and cerebrovascular disease, and the condition is unstable or uncontrollable.
• Already known active central nervous system metastasis and/or cancerous meningitis. Subjects with stable brain metastases after previous treatment may participate as long as no radiologic evidence of progression lasts for at least four weeks prior to this trial and any neurological symptoms have returned to baseline, and no new or enlarged metastatic evidence in brain and no steroids use for at least 7 days prior to trial treatment. Cancer meningitis should be excluded regardless of clinical stability.
• Surgery was performed within 4 weeks prior to the trial and patients must be
• evaluated after wound healing.
• Hepatic and renal dysfunction evidence: jaundice, ascites, and/or bilirubin ≥ 1.5 × ULN, and/or alkaline phosphatase ≥ 3 × ULN, and/or ≥ 3 grade (CTC-AE 5.0) proteinuria (\> 3.5g /24 hours), or renal failure requiring blood dialysis or peritoneal dialysis.
• Urine examination shows urinary protein ≥ ++ or 24 hours urine protein \>1.0g. Persistent \>2 grade (CTCAE5.0) infection.
• History of allogeneic tissue transplantation or solid organ transplantation.

Sponsors & Collaborators

• Wan-Guang Zhang: lead
• Chinese Cooperative Group of Liver Cancer: collaborator
• Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province: collaborator
• M&R Pharm: collaborator
• Geneplus-Beijing Co. Ltd.: collaborator
• Yuce Biotechnology Co., Ltd.: collaborator
• Geneis: collaborator
• Simcere Pharmaceutical Co., Ltd: collaborator
• BeiGene: collaborator
• Haplox Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

cell wall skeleton, Nocardia; lenvatinib; tislelizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Wan-guang Zhang, M.D.

  Tongji Hospital

  STUDY CHAIR

Central Study Contacts

Wan-guang Zhang, M.D.

CONTACT

86-27-83665213; wgzhang@tjh.tjmu.edu.cn

Ze-yang Ding, M.D.

CONTACT

86-27-69378710; zyding@tjh.tjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Executive Deputy Director of Hepatic Surgery Center

Study Record Dates

• First Submitted: September 4, 2022
• First Posted: September 9, 2022
• Study Start: September 1, 2022
• Primary Completion: August 31, 2024
• Study Completion: February 28, 2025
• Last Updated: December 19, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)