Valuation of the Safety and Efficacy of Combination of Cryoablation and Dendric Cell/Cytokine-induced Killers Cells Treatment for Advanced Liver Cancers

NCT05622825 | Unknown Phase 1

• 1 other identifier: 202112056DIPC
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief Summary

The treatment of liver cancer needs integrated medical strategies, including surgery, chemotherapy, target therapy, radiotherapy, and immunotherapy. According to the patient's condition to develop a personalized and best treatment plan. Cryoablation can produce osmotic shock through repeated freeze-thaw to cause tumor cell necrosis, and release tumor antigens to activate anti-tumor immune responses. Immune cell therapy is an emerging field across cancer types in current cancer treatment. This study desired to combine cryotherapy and cellular immunotherapy to achieve the effect of tumor control. In recent years, cancer treatment studies have showed that cryoablation combined with immune cell therapy can play a good auxiliary effect and improve the cancer treatment efficacy significantly. This trial study is a single center, single-arm, non-blind open-label human clinical trial. To explore the therapeutic effect and safety of cryoablation combined with autologous DC-CIK (through hepatic artery infusion, HAI) for patients with advanced liver cancers. The DC-CIK biologics are provided by BOHUI Biotech company. Their core technology (including clinical treatment and cell culture techniques) was transferred from Dr. Hasumi who is a Japanese clinician and this technical founder.

Conditions

Advanced Liver Cancers

Keywords

DC-CIK; Cryoablation; Advanced Liver Cancers

Outcome Measures

Primary Outcomes (1)

• Image Assessment

  Evaluation of the treatment outcome using computed tomography (CT or PET/CT) or magnetic resonance imaging (MRI) to facilitate comparison of pre- and post-treatment differences. Response Evaluation Criteria in Solid tumor (RECIST criteria) will be used to evaluate the treatment effect of target lesions after treatment. The RECIST criteria will calculate Disease Control Rate.

  6 weeks after treatment

Secondary Outcomes (2)

• Quality of life assessment.

  12 weeks after treatment

• Quality of life assessment.

  12 weeks after treatment

Study Arms (1)

cryoablation combined DC-CIK

EXPERIMENTAL

To explore the therapeutic effect and safety of cryoablation combined with autologous DC-CIK (through hepatic artery infusion, HIA) for patients with advanced liver cancers

Biological: DC-CIK

Interventions

DC-CIK BIOLOGICAL

To explore the therapeutic effect and safety of cryoablation combined with autologous DC-CIK (through hepatic artery infusion, HIA) for patients with advanced liver cancers

cryoablation combined DC-CIK

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged between 20 and 80 years old.
• Patients with advanced stage hepatocellular carcinoma or advanced stage hepatic metastasis derived from extrahepatic primary carcinoma, who are judged as advanced stage by clinical criteria (The Eighth Edition AJCC Cancer Staging Manual) through pathology and imaging reports.
• Patients who have been evaluated by a physician for benefits and risks and are no longer considered suitable for previous third-line therapies will be included in this trial.
• There is at least one target lesion larger than 1.0 cm that can be measured by MRI or CT and is appropriately located for cryoablation by imaging.
• Child-Pugh class (A or B).
• Adequate bone marrow function (white blood cell count \> 2x109/L, platelet count \> 5x1010/L).
• coagulation function: prothrombin time (PT), activated partial thromboplastin time (APTT) ≤ 1.5 times the upper limit of normal
• renal function: blood creatinine concentration (creatinine) \< 1.5 mg/dL .
• Karnofsky Performance Status (KPS) score70 -10.
• maximum tumor diameter ≤ 5 cm
• number of tumors ≤ 5
• Survival period greater than 3 months as predicted by the physician.

You may not qualify if:

• Tumor size \>5 cm in diameter or tumor number \>5.
• not suitable for cytarabine or cryoablation as determined by the trial physician.
• Blood screening for any of the following viral infections: human immunodeficiency virus, human T-lymphotropic virus, syphilis, hepatitis B virus, hepatitis C virus, cytomegalovirus IgM antibody positive, etc.
• Previous treatment prior to screening: Chemotherapy or radiation therapy must be completed before 3 weeks of screening to avoid systemic immune responses interfering with the immune cell therapy. If participating in clinical trials of other biologic agents or immunotherapy, at least 4 weeks of screening is required.
• Patient is acutely or chronically infected or in acute cytomegalovirus attack at the time of screening.
• Patients with level 3 hypertension, or patients with severe coronary disease.
• patients with autoimmune disease.
• patients who are pregnant, breastfeeding, or unable to use effective contraception.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Related Publications (12)

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• Pievani A, Borleri G, Pende D, Moretta L, Rambaldi A, Golay J, Introna M. Dual-functional capability of CD3+CD56+ CIK cells, a T-cell subset that acquires NK function and retains TCR-mediated specific cytotoxicity. Blood. 2011 Sep 22;118(12):3301-10. doi: 10.1182/blood-2011-02-336321. Epub 2011 Aug 5.

  PMID: 21821703 BACKGROUND

• Cappuzzello E, Sommaggio R, Zanovello P, Rosato A. Cytokines for the induction of antitumor effectors: The paradigm of Cytokine-Induced Killer (CIK) cells. Cytokine Growth Factor Rev. 2017 Aug;36:99-105. doi: 10.1016/j.cytogfr.2017.06.003. Epub 2017 Jun 3.

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• Yakkala C, Chiang CL, Kandalaft L, Denys A, Duran R. Cryoablation and Immunotherapy: An Enthralling Synergy to Confront the Tumors. Front Immunol. 2019 Sep 24;10:2283. doi: 10.3389/fimmu.2019.02283. eCollection 2019.

  PMID: 31608067 BACKGROUND

• Yuanying Y, Lizhi N, Feng M, Xiaohua W, Jianying Z, Fei Y, Feng J, Lihua H, Jibing C, Jialiang L, Kecheng X. Therapeutic outcomes of combining cryotherapy, chemotherapy and DC-CIK immunotherapy in the treatment of metastatic non-small cell lung cancer. Cryobiology. 2013 Oct;67(2):235-40. doi: 10.1016/j.cryobiol.2013.08.001. Epub 2013 Aug 13.

  PMID: 23948179 BACKGROUND

• Liu Y, Liu H, Liu H, He P, Li J, Liu X, Chen L, Wang M, Xi J, Wang H, Zhang H, Zhu Y, Zhu W, Ning J, Guo C, Sun C, Zhang M. Dendritic cell-activated cytokine-induced killer cell-mediated immunotherapy is safe and effective for cancer patients >65 years old. Oncol Lett. 2016 Dec;12(6):5205-5210. doi: 10.3892/ol.2016.5337. Epub 2016 Nov 2.

  PMID: 28105230 BACKGROUND

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  PMID: 28508945 BACKGROUND

• Hasumi K, Aoki Y, Wantanabe R, Mann DL. Clinical response of advanced cancer patients to cellular immunotherapy and intensity-modulated radiation therapy. Oncoimmunology. 2013 Oct 1;2(10):e26381. doi: 10.4161/onci.26381. Epub 2013 Oct 17.

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Central Study Contacts

Kai-Wen Huang, MD, PhD

CONTACT

+886-23123456; fangyu0429@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients must receive 2 DC/AT hepatic artery infusion and be treated with cryoablation technique. Phase Ⅰ The first 3 subjects were enrolled by Sequential enrollment. The next subject can be enrolled only after the first subject has completed the return transfusion and the safety assessment (V7). After the sixth subject completes the safety assessment (V7), the next nine subjects can be enrolled in phase IIA of the trial to evaluate the efficacy of the trial. If less than two of the first six subjects have a Common Terminology Criteria for Adverse Events (CTCAE) v5.0 level 3 or higher adverse event related to the test drug Phase Ⅱ Phase IIA to evaluate the efficacy and implementation. However, if two of the first six subjects have a Grade 3 or higher trial drug-related adverse event or one or more deaths, the trial will be terminated immediately and all cell product process-related factors in this trial will be fully investigated.

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: November 21, 2022
• Study Start: January 1, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: November 21, 2022

Record last verified: 2022-10