Trial Title:
Nocardia Rubra Cell Wall Skeleton (N-CWS) Plus HAIC, Lenvatinib and Tislelizumab in Treating Patients With Advanced HCC
NCT ID:
NCT05533892
Condition:
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Lenvatinib
Tislelizumab
Cell Wall Skeleton
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Nocardia rubra cell wall skeleton
Description:
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)
Arm group label:
Nocardia rubra cell wall skeleton (N-CWS) Plus HAIC, Lenvatinib and Tislelizumab
Other name:
N-CWS
Intervention type:
Procedure
Intervention name:
Hepatic arterial infusion chemotherapy
Description:
administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding
arteries every 3 weeks
Arm group label:
Nocardia rubra cell wall skeleton (N-CWS) Plus HAIC, Lenvatinib and Tislelizumab
Other name:
HAIC
Intervention type:
Drug
Intervention name:
Lenvatinib
Description:
12 mg (or 8 mg) once daily (QD) oral dosing
Arm group label:
Nocardia rubra cell wall skeleton (N-CWS) Plus HAIC, Lenvatinib and Tislelizumab
Other name:
JieLiEn
Intervention type:
Drug
Intervention name:
Tislelizumab
Description:
200mg intravenously every 3 weeks
Arm group label:
Nocardia rubra cell wall skeleton (N-CWS) Plus HAIC, Lenvatinib and Tislelizumab
Other name:
BaiZeAn
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).
Criteria for eligibility:
Criteria:
Inclusion Criteria: Subjects must meet all of the following criteria
- 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.
- Biochemical examination (no ALB infused within 14 days): ALB≥29 g/L, ALT and
AST<5×ULN, TBIL≤1.5×ULN, creatinine≤1.5×ULN (only one of albumin and bilirubin has 2
points with Child-Pugh score).
- Tumor tissue must be available for biomarker analysis prior to the first dose of
treatment, If not available, participants can consult the investigator for
enrollment agreement.
- Note: If an unstained section is submitted, the new section should be submitted to
the laboratory within 14 days.
Exclusion Criteria: Subjects with one or more than one of the following criteria should
be excluded
- 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.
- History of active tuberculosis, such as mycobacterium tuberculosis.
- Intolerant of any drug (or any excipient) in this trial.
- Female patients who are pregnant, breastfeeding or refuse contraception.
- Known or untreated brain metastases, or patients with epilepsy who need medication
treatment.
- Patients with bone metastases received palliative radiotherapy (radiation area > 5%
bone marrow area) within 4 weeks prior to this study, or there were wounds, ulcers
or fractures that could not be healed, or patients have organ transplantation
history.
- Gastrointestinal bleeding history in the past 6 months or tendency to
gastrointestinal bleeding, such as esophageal varices, local active ulceration
lesions, fecal occult blood ≥ (++) (gastroscopy is required when fecal occult blood
is (+)).
- Evidence or history of ≥3 grade (CTCAE5.0) bleeding events.
- History of human immunodeficiency virus infection.
- History of hepatitis B virus or hepatitis C virus infection, and not receive regular
treatment.
- Severe non-healing wounds, ulcers or fractures.
- Prior treatment with either lenvatinib or any kind of anti-PD-1, anti-PD-L1 or
anti-PD-L2 drugs.
- There were no active autoimmune diseases that require systemic treatment such as
disease modifying drugs, corticosteroids or immunosuppressants in the past 2 years.
Alternative therapies with thyroxine, insulin or corticosteroid are not considered
as systemic therapy.
- Diagnosis of immunodeficiency or systemic steroid therapy or any form of
immunosuppressants therapy within 7 days prior to this study. A physiological dose
of corticosteroids (no more than 7.5 mg/d prednisone or equivalent) can be approved
after clinical evaluation.
- There exists drug abuse, or any medical, psychological or social condition which
might affect the study, the compliance or even the safety of patients.
- Variable factors which significantly affect drug use and absorption, such as
inability to swallow, chronic diarrhea and intestinal obstruction.
- Any >1 grade (CTC-AE5.0) unresolved toxicity due to previous treatment or operation,
except for hair loss, anemia, and hypothyroidism.
- Vaccination of any live virus vaccine within 30 days prior to this study, except for
seasonal flu vaccines without live virus.
- 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.
- Women with fertility agree to abstinence during the treatment period and at least 6
months after the last dose (avoiding heterosexual intercourse) or using a
contraceptive method with an annual contraceptive failure rate <1%.
- If a female patient has menstruation and not reached the postmenopausal state
(continuously no menstruation ≥ 12 months and no other causes), and has not
undergone sterilization by removing the ovaries and/or uterus), then the patient has
fertility.
- Contraceptive methods with a contraceptive failure rate <1% include bilateral tubal
ligation, male sterilization, hormonal contraceptives that inhibit ovulation,
hormone-releasing intrauterine devices and copper intrauterine devices.
- The reliability of sexual desire should be evaluated relative to the duration of the
clinical trial and lifestyle of patient. Periodic abstinence (eg. calendar days,
ovulation, symptomatic body temperature or post-ovulation methods) and in vitro
ejaculation are unacceptable methods of contraception.
- Male patients agree to abstinence (no heterosexual intercourse) or use of
contraceptive measures and no sperm donation, as defined below:
- When a female partner has fertility, male patients must abstinence from sex during
treatment and at least 6 months after the last dose of treatment, or use condoms and
other contraceptive methods with contraceptive failure rate <1%. At the same time,
male patients must also agree not to donate sperm.
- When a female partner is pregnant, the male patient must abstinence or using a
condom during the treatment period and at least 6 months after the last dose of
treatment to prevent the fetus from being affected by the study.
- The reliability of sexual desire should be evaluated relative to the duration of the
clinical trial and lifestyle of patient. Periodic abstinence (eg. calendar days,
ovulation, symptomatic body temperature or post-ovulation methods) and in vitro
ejaculation are unacceptable methods of contraception.
- Patients are unsuitable for participation in this research after comprehensive
assessment by the researchers.
- Patients participate in another clinical study at the same time.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Address:
City:
Wuhan
Zip:
430030
Country:
China
Status:
Recruiting
Contact:
Last name:
Wan-guang Zhang, M.D.
Phone:
86-27-83665213
Email:
wgzhang@tjh.tjmu.edu.cn
Contact backup:
Last name:
Ze-yang Ding, M.D.
Phone:
86-27-69378710
Email:
zyding@tjh.tjmu.edu.cn
Start date:
September 1, 2022
Completion date:
February 28, 2025
Lead sponsor:
Agency:
Wan-Guang Zhang
Agency class:
Other
Collaborator:
Agency:
Chinese Cooperative Group of Liver Cancer
Agency class:
Other
Collaborator:
Agency:
Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province
Agency class:
Other
Collaborator:
Agency:
M&R Pharm
Agency class:
Other
Collaborator:
Agency:
Geneplus-Beijing Co. Ltd.
Agency class:
Industry
Collaborator:
Agency:
Yuce Biotechnology Co., Ltd.
Agency class:
Other
Collaborator:
Agency:
Geneis
Agency class:
Other
Collaborator:
Agency:
Simcere Pharmaceutical Co., Ltd
Agency class:
Other
Collaborator:
Agency:
BeiGene
Agency class:
Industry
Collaborator:
Agency:
Haplox Biotechnology Co., Ltd.
Agency class:
Industry
Source:
Tongji Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05533892
