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Cancer Biology & Medicine 2023, 20(6): 465-476 https://doi.org/10.20892/j.issn.2095-3941.2022.0762
Original Article | Open Access | Issue | Published: 22 June 2023

Phase Ⅰ study of chlorogenic acid injection for recurrent high-grade glioma with long-term follow-up

Show Author's Information Zhuang Kang1,*,  Shan Li2,*,  Xun Kang1,  Jing Deng3,  Huarong Yang3,  Feng Chen1,  Jiandong Jiang4,  Jie Zhang3( ),  Wenbin Li1 ( )
Department of Neuro-oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
Sichuan Jiuzhang Biological Science and Technology Co. Ltd, Chengdu 610095, China
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100070, China

*Zhuang Kang and Shan Li contributed equally to this work.

Keywords:
Recurrent high-grade glioma, chlorogenic acid (CGA), temozolomide (TMZ)
Cite this article:
Kang Z, Li S, Kang X, et al. Phase Ⅰ study of chlorogenic acid injection for recurrent high-grade glioma with long-term follow-up. Cancer Biology & Medicine, 2023, 20(6): 465-476. https://doi.org/10.20892/j.issn.2095-3941.2022.0762
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Abstract Full text Electronic supplementary material About this article
Objective

This study was aimed at analyzing the efficacy and safety of an injectable form of chlorogenic acid (CGA) in patients with recurrent high-grade glioma after standard of care treatments, through a first-in-human, open-label, dose-escalation phase Ⅰ trial.

Methods

A total of 26 eligible patients were enrolled, received intramuscular CGA injections at 5 dose levels, and were followed up for 5 years. CGA was well tolerated, and the maximum tolerated dose was 5.5 mg/kg.

Results

The most common treatment-related adverse events occurred at the sites of injection. No grade 3 or 4 adverse events (e.g., drug allergy) were reported for these patients except for induration at the injection sites. A clinical pharmacokinetic study showed that CGA was rapidly eliminated from the plasma, with a t1/2 of 0.95-1.27 h on day 1 and 1.19-1.39 h on day 30, and no detectable CGA was observed on days 9, 11, 13, 23, 25, 27, and 29 before CGA administration. After the first treatment cycle, 52.2% of patients (12 of 23) achieved stable disease. Long-term follow-up indicated an estimated median overall survival of 11.3 months for all 23 evaluable patients. Of the 18 patients with grade 3 glioma, the median overall survival was 9.5 months. Two patients remained alive at the cutoff day.

Conclusions

This phase Ⅰ study demonstrated that CGA has a favorable safety profile (with no severe toxicity), and provides preliminary clinical benefits for patients with high grade glioma relapsing after prior standard therapies, thus shedding light on the potential clinical application of CGA for recurrent grade 4 glioma.


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Abstract
Full text
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Electronic supplementary material
About this article

Phase Ⅰ study of chlorogenic acid injection for recurrent high-grade glioma with long-term follow-up

Show Author's information Zhuang Kang1,*, Shan Li2,*, Xun Kang1, Jing Deng3, Huarong Yang3, Feng Chen1, Jiandong Jiang4, Jie Zhang3( ), Wenbin Li1 ( )
Department of Neuro-oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
Sichuan Jiuzhang Biological Science and Technology Co. Ltd, Chengdu 610095, China
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100070, China

*Zhuang Kang and Shan Li contributed equally to this work.

Abstract

Objective

This study was aimed at analyzing the efficacy and safety of an injectable form of chlorogenic acid (CGA) in patients with recurrent high-grade glioma after standard of care treatments, through a first-in-human, open-label, dose-escalation phase Ⅰ trial.

Methods

A total of 26 eligible patients were enrolled, received intramuscular CGA injections at 5 dose levels, and were followed up for 5 years. CGA was well tolerated, and the maximum tolerated dose was 5.5 mg/kg.

Results

The most common treatment-related adverse events occurred at the sites of injection. No grade 3 or 4 adverse events (e.g., drug allergy) were reported for these patients except for induration at the injection sites. A clinical pharmacokinetic study showed that CGA was rapidly eliminated from the plasma, with a t1/2 of 0.95-1.27 h on day 1 and 1.19-1.39 h on day 30, and no detectable CGA was observed on days 9, 11, 13, 23, 25, 27, and 29 before CGA administration. After the first treatment cycle, 52.2% of patients (12 of 23) achieved stable disease. Long-term follow-up indicated an estimated median overall survival of 11.3 months for all 23 evaluable patients. Of the 18 patients with grade 3 glioma, the median overall survival was 9.5 months. Two patients remained alive at the cutoff day.

Conclusions

This phase Ⅰ study demonstrated that CGA has a favorable safety profile (with no severe toxicity), and provides preliminary clinical benefits for patients with high grade glioma relapsing after prior standard therapies, thus shedding light on the potential clinical application of CGA for recurrent grade 4 glioma.

Keywords: Recurrent high-grade glioma, chlorogenic acid (CGA), temozolomide (TMZ)

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Publication history

Received: 21 December 2022
Accepted: 24 April 2023
Published: 22 June 2023
Issue date: June 2023

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©2023 Cancer Biology & Medicine.

Acknowledgements

Acknowledgements

The authors and sponsors thank the patients and their families, as well as the participating study team, for making this study possible. We also thank Dr. Jing Deng for critically reviewing the manuscript.

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