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Safety and Efficacy of Bifidobacterium Therapy in Patients With Advanced Liver Cancer Receiving Immunotherapy

Sponsor
Sun Yat-sen University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05620004
Collaborator
(none)
30
Enrollment
1
Location
2
Arms
36
Anticipated Duration (Months)
0.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study plans to observe the changes of liver cancer and immune cell subsets by replicating the high abundance intestinal flora and liver cancer mouse model, reveal the relationship and mechanism of intestinal flora in the immunotherapy of liver cancer, and study the impact on prognosis by regulating the positive correlation of lactic acid bacteria and bifidobacteria of rumen coccus in patients with advanced liver cancer receiving immunotherapy

Condition or Disease Intervention/Treatment Phase
  • Drug: Bifidobacterium Bifidum Oral Product
 Phase 1/Phase 2

Detailed Description

Select patients with advanced hepatocellular carcinoma who have been clinically consulted by MDT,those patients will be treated with carrilizumab and apatinib mesylate, and divide them into two groups randomly .Collect the stool specimens and clinical data from those who will be treated with oral bifidobacterium or without bifidobacterium during immunotherapy.; Use 16S sequencing to detect the changes in the composition ratio of intestinal flora and the level of galactose acid, judge the response to clinical treatment and establish the relationship curve with clinical treatment efficacy.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Select patients with advanced hepatocellular carcinoma who have been clinically consulted by MDT ,those patients will be treated with carrilizumab and apatinib mesylate,and divide them into two groups randomly .Collect the stool specimens and clinical data from those who will be treated with oral bifidobacterium or without bifidobacterium during immunotherapy.Select patients with advanced hepatocellular carcinoma who have been clinically consulted by MDT ,those patients will be treated with carrilizumab and apatinib mesylate,and divide them into two groups randomly .Collect the stool specimens and clinical data from those who will be treated with oral bifidobacterium or without bifidobacterium during immunotherapy.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Safety and Efficacy of Bifidobacterium Therapy in Patients With Advanced Liver Cancer Receiving Immunotherapy: a Randomized Controlled, Single-center Clinical Trial
Actual Study Start Date :
Nov 1, 2021
Anticipated Primary Completion Date :
Dec 31, 2023
Anticipated Study Completion Date :
Oct 31, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Bifidobacterium Bifidum Oral Product

patients with advanced hepatocellular carcinoma who will be treate with carrilizumab and apatinib mesylate plus Bifidobacterium Bifidum Oral Product daily

Drug: Bifidobacterium Bifidum Oral Product
experimental group use Bifidobacterium Bifidum Oral Product and control group without Bifidobacterium Bifidum Oral Product
Other Names:
  • LiveCombinedBifidobacterium,LactobacillusandStreptococcusthermophilusTablets,Oral

    		•
    No Intervention: without Bifidobacterium Bifidum Oral Product

    patients with advanced hepatocellular carcinoma who will be treate with carrilizumab and apatinib mesylate without Bifidobacterium Bifidum Oral Product daily

    Outcome Measures

    Primary Outcome Measures

    1. objective response rate(ORR) [1 year]

      The proportion of patients with tumor volume reduction up to a pre-specified value and able to maintain the minimum time requirement is the sum of the proportion in complete and partial remission

    2. disease control rate(DCR) [1 year]

      The number of cases with remission and stable lesions after treatment as a percentage of evaluable cases that were maintained for at least 4 weeks.

    3. overall survival(OS) [1 year]

      The time interval from the start of treatment until the patient's death (from any cause)

    4. progression-free survival(PFS) [1 year]

      Time interval from the start of treatment until disease progression (including death)

    5. Number of participants with treatment-related adverse events as assessed by NCI-CTCAE 5.0." [1 year]

      Side effects due to immunotherapy

    Secondary Outcome Measures

    1. Change in tumor volume before and after treatment [24 weeks]

      The efficacy of the study will be evaluated based on the imaging results and evaluation criteria for efficacy of solid tumorssolid tumors (RECISTv1.1).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Patients with HCC diagnosed by pathological histology or cytology or clinically confirmed.

    2. Expected survival ≥ 12 weeks.

    3. No systemic systemic antitumor therapy against hepatocellular carcinoma prior to the first dose.

    4. Child-Pugh liver function rating: Grade A or B (≤7 points).

    5. Stage IIIa: regardless of tumor status, with vascular invasion, no extrahepatic metastasis; liver function grade Child-Pugh A/B; PS 02, IIIb: regardless of tumor status, regardless of vascular invasion, with extrahepatic metastasis; liver function grade Child-Pugh A/B; PS 02. Not Stage B not suitable for radical surgery and/or local treatment.

    6. ECOG physical status score ≤2.

    7. At least one measurable lesion according to RECIST v1.1 (measurable lesion spiral CT tracing length ≥ 10 mm or enlarged lymph node short diameter ≥ 15 mm)

    8. Routine blood tests: (no blood transfusion, G-CSF medication correction within 14 days prior to screening)

    9. Laboratory test values within 7 days prior to enrollment meet the following requirements (no blood components, cell growth factors, albumin, or other corrective therapies are allowed within the first 14 days of obtaining laboratory tests), as follows.

    ① Blood count: absolute neutrophil count (ANC) ≥ 1.5×109/L; platelet count (PLT) ≥ 75×109/L; hemoglobin level (HGB) ≥ 9.0 g/dL.

    ② Liver function: serum total bilirubin (TBIL) ≤2× upper limit of normal (ULN); alanine amino transferase (ALT) and aspartate aminotransferase (ST) ≤5×ULN; serum albumin ≥28 g/L; alkaline phosphatase (ALP) ≤5×ULN.

    (iii) Renal function: serum creatinine (Cr) ≤ 1.5×ULN or creatinine clearance (CCr) ≥ 50 mL/min (Cockcroft-Gault formula); urine routine results show urine protein <2+; for patients with urine protein ≥2+ at baseline, 24-hour urine collection and 24-hour urine protein quantification <1g should be performed.

    ④ Coagulation: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 times ULN.

    1. Female patients of childbearing age or male patients whose sexual partners are women of childbearing age are required to use effective contraception throughout the treatment period and for 6 months after the last dose.

    2. Sign a written informed consent form and be able to comply with protocol visits and related procedures.

    Exclusion Criteria:

    1. Patients with hepatocellular carcinoma who have received prior treatment with carrilizumab or any other PD-L1 or PD-1 antagonist, or who have participated in a phase III study with apatinib after receiving systemic therapy.

    2. Subjects with any active autoimmune disease or history of autoimmune disease, including but not limited to: hepatitis, pneumonia, uveitis, colitis (inflammatory bowel disease), pituitary inflammation, vasculitis, nephritis, hyperthyroidism and hypothyroidism, except vitiligo or resolved childhood asthma/atopic disease. Patients with asthma requiring intermittent use of bronchodilators or other medical interventions should also be excluded.

    3. Subjects with systemic or absorbable topical corticosteroids requiring immunosuppressive drugs or immunosuppressive doses. Prednisone or equivalent doses greater than 10 mg/day are contraindicated for 2 weeks prior to dosing. Corticosteroids for intravenous contrast allergy prophylaxis are permitted.

    4. Persons with known or suspected allergic reactions to any component of the Karelixu formulation.

    5. Central nervous system (CNS) metastases with clinical signs (including cerebral edema, steroid requirements, or progressive disease). Subjects receiving treatment for brain or meningeal metastases must be clinically stable (no evidence of new or enlarged metastases on magnetic resonance imaging [MRI] at least 4 weeks apart) and have discontinued treatment with systemic steroid immunosuppressive doses (>10 mg/day of prednisone or equivalent) at least 2 weeks prior to study drug.

    6. Other malignancies (except cured basal cell carcinoma of the skin and cervical cancer)

    7. Clinically significant cardiovascular disease, including but not limited to: severe acute myocardial infarction, unstable or severe angina, coronary artery bypass surgery, congestive heart failure (New York Heart Association (NYHA) class >2), ventricular arrhythmia requiring medical intervention, and left ventricular ejection fraction (LVEF) <50% within 6 months prior to enrollment.

    8. Poorly controlled hypertension within 3 months: systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg.

    9. Subjects with bleeding tendency or on thrombolytic or anticoagulant therapy.

    10. Subjects who have received systemic chemotherapy, radiotherapy, immunotherapy, hormonal therapy, surgery, or targeted therapy within 4 weeks (or equivalent to 5 half-lives, whichever is greater) prior to dosing or have any unresolved adverse event

    Common Terminology Criteria for Adverse Events (CTCAE) Level 1 (allowing for unresolved stable chronic toxicity).

    1. Subjects with clinically symptomatic ascites or pleural effusion that remains uncontrolled by therapeutic puncture and drainage.

    2. History of gastrointestinal bleeding within 3 months or significant tendency to gastrointestinal bleeding such as: esophageal varices, locally active ulcerative lesions, gastric and duodenal ulcers, ulcerative colitis or gastrointestinal diseases such as portal hypertension or tumor resection with risk of bleeding

    3. Severe bleeding (bleeding >30 ml within 3 months), hemoptysis (>5 ml within 4 weeks) or thromboembolic events (within 12 months, including stroke events and/or transient ischemic attacks).

    4. Active infection or fever of unknown origin >38.5°C during the screening visit or on the first scheduled dosing date (patients with fever due to tumor may be included at the discretion of the investigator)

    5. History of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, or severely impaired lung function.

    6. History of immunodeficiency including human immunodeficiency virus (HIV) positive, or other acquired or congenital immunodeficiency disease, or active hepatitis (transaminases not meeting inclusion criteria, hepatitis B virus (HBV) DNA ≥ 104/ml or hepatitis C virus (HCV) RNA ≥ 103/ml (or higher). Chronic hepatitis B virus carriers with HBV DNA <2000 IU/ml (<104/ml) must receive antiviral therapy throughout the study.

    7. Subjects who have participated in other clinical trials or completed other clinical trials within 4 weeks.

    8. Subjects who may be receiving other anti-tumor systemic therapy during the study.

    9. Subjects who may have received a vaccine during the study period or who have previously received a vaccine within 4 weeks.

    10. History of psychiatric disorder or psychotropic substance abuse.

    11. Any other medical, psychiatric or social condition that, in the opinion of the investigator, may affect the subject's rights, safety, welfare or ability to sign informed consent, cooperate and participate in the study or interfere with the interpretation of the results.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou Guangdong China 510630

    Sponsors and Collaborators

    • Sun Yat-sen University

    Investigators

    • Principal Investigator: Chan Xie, PhD, Third Affiliated Hospital, Sun Yat-Sen University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Chan Xie, associate chief physician, Sun Yat-sen University
    ClinicalTrials.gov Identifier:
    NCT05620004
    Other Study ID Numbers:
    • XC4
    First Posted:
    Nov 17, 2022
    Last Update Posted:
    Nov 17, 2022
    Last Verified:
    Nov 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Chan Xie, associate chief physician, Sun Yat-sen University
    Advanced Hepatocellular Carcinoma
    Immunotherapy
    Bifidobacterium
    Additional relevant MeSH terms:
    Carcinoma, Hepatocellular
    Liver Neoplasms

    Study Results

    No Results Posted as of Nov 17, 2022