Phase I study to evaluate the maximum tolerated dose of the combination of SH003 and docetaxel in patients with solid cancer: A study protocol

Chunhoo Cheon, Seong-Gyu Ko, Chunhoo Cheon, Seong-Gyu Ko

Abstract

Introduction: Cancer is the second leading cause of death, and the burden of cancer continues to grow globally. Research on the efficacy of combined administration of herbal medicine and anticancer drugs is also increasing. SH003 is a new herbal medicine composed of Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii. SH003 alone up to 4800 mg daily was found to be safe. Preclinical studies have shown SH003 to have a synergistic effect with coadministration of anticancer drugs. This study aimed to determine the maximum tolerated dose of SH003 combined with docetaxel in patients with lung or breast cancer.

Methods: This is an open-label, dose-escalation study to evaluate the safety of SH003 combined with docetaxel. Patients with lung or breast cancer will be recruited. The participants will be divided into 3 groups based on SH003 daily dose (2400, 3600, and 4800 mg); the medication will be taken orally for 21 days. The traditional 3 + 3 design will be adopted for the dose escalation. Dose-limiting toxicities are defined as grade 3 or 4 adverse events according to the Common Terminology Criteria for Adverse Events. The highest dose at which no more than 1 of the 6 patients experience dose-limiting toxicity will be determined as the maximum tolerated dose of SH003 combined with docetaxel.

Discussion: This study investigates the safety of SH003 when combined with docetaxel. The results of this study will provide a safe dose range for conducting therapeutic exploratory trials.

Trial registrations: ClinicalTrials.gov NCT04360317.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Study flow chart.

References

    1. World Health Organization Cancer, Fact Sheet. 2018;. Accessed July 6, 2020.
    1. Copur MS. State of cancer research around the globe. Oncology (Williston Park) 2019;33:181–5..
    1. Peng F, Xie X, Peng C. Chinese herbal medicine-based cancer therapy: novel anticancer agents targeting microRNAs to regulate tumor growth and metastasis. Am J Chin Med 2019;47:1711–35..
    1. Park CR, Lee JS, Son CG, et al. A survey of herbal medicines as tumor microenvironment-modulating agents. Phytother Res 2020. 1–7..
    1. Li Y, Li X, Cuiping C, et al. Study on the anticancer effect of an astragaloside- and chlorogenic acid-containing herbal medicine (RLT-03) in breast cancer. Evid Based Complement Alternat Med 2020;2020:1515081.
    1. Chung VC, Wu X, Lu P, et al. Chinese herbal medicine for symptom management in cancer palliative care: systematic review and meta-analysis. Medicine (Baltimore) 2016;95:e2793.
    1. Lee YK, Bae K, Yoo HS, et al. Benefit of adjuvant traditional herbal medicine with chemotherapy for resectable gastric cancer. Integr Cancer Ther 2018;17:619–27..
    1. Bae K, Park JH, Kim J, et al. Traditional oriental herbal medicine and natural killer cells for cancer patients: a systematic review and meta-analysis. Phytother Res 2017;31:519–32..
    1. Liu Y, May BH, Zhang AL, et al. Integrative herbal medicine for chemotherapy-induced peripheral neuropathy and hand-foot syndrome in colorectal cancer: a systematic review and meta-analysis. Integr Cancer Ther 2019;18: 1534735418817833.
    1. National College of Korean Medicine Publication Committee on Joint Textbook Herbology. Seoul, Korea: Younglimsa; 2016.
    1. Choi YK, Cho SG, Woo SM, et al. Herbal extract SH003 suppresses tumor growth and metastasis of MDA-MB-231 breast cancer cells by inhibiting STAT3-IL-6 signaling. Mediators Inflamm 2014;2014:492173.
    1. Choi YK, Cho SG, Choi YJ, et al. SH003 suppresses breast cancer growth by accumulating p62 in autolysosomes. Oncotarget 2016;8:88386–400..
    1. Choi YJ, Choi YK, Lee KM, et al. SH003 induces apoptosis of DU145 prostate cancer cells by inhibiting ERK-involved pathway. BMC Complement Altern Med 2016;16:507.
    1. Choi HS, Kim MK, Lee K, et al. SH003 represses tumor angiogenesis by blocking VEGF binding to VEGFR2. Oncotarget 2016;7:32969–79..
    1. Choi EK, Kim SM, Hong SW, et al. SH003 selectively induces p73-dependent apoptosis in triple-negative breast cancer cells. Mol Med Rep 2016;14:3955–60..
    1. Lee KM, Lee K, Choi YK, et al. SH003 induced G1 phase cell cycle arrest induces apoptosis in HeLa cervical cancer cells. Mol Med Rep 2017;16:8237–44..
    1. Cheon C, Kang S, Ko Y, et al. Single-arm, open-label, dose-escalation phase I study to evaluate the safety of a herbal medicine SH003 in patients with solid cancer: a study protocol. BMJ Open 2018;8:e019502.
    1. Cheon C, Ko SG. A phase I study to evaluate the safety of the herbal medicine SH003 in patients with solid cancer. Integr Cancer Ther 2020;19: 1534735420911442.
    1. Woo SM, Kim AJ, Choi YK, et al. Synergistic effect of SH003 and doxorubicin in triple-negative breast cancer. Phytother Res 2016;30:1817–23..
    1. Choi HS, Cho SG, Kim MK, et al. SH003 enhances paclitaxel chemosensitivity in MCF-7/PAX breast cancer cells through inhibition of MDR1 activity. Mol Cell Biochem 2017;426:1–8..
    1. National Breast Cancer Centre Clinical Practice Guidelines for the Management of Early Breast Cancer. 2nd ed. Canberra: Commonwealth of Australia; 2001.
    1. Alqahtani FY, Aleanizy FS, El Tahir E, et al. Paclitaxel. Profiles Drug Subst Excip Relat Methodol 2019;44:205–38..
    1. Cortes JE, Pazdur R. Docetaxel. J Clin Oncol 1995;13:2643–55..
    1. U.S. Department of Health and Human Services Common Terminology Criteria for Adverse Events (CTCAE) v5.0. 2017.
    1. Storer BE. An evaluation of phase I clinical trial designs in the continuous dose-response setting. Stat Med 2001;20:2399–408..
    1. U.S. Dept. of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. In. Rockville, MD. 2005.
    1. WHO Collaborating Centre for Evidence-Based Research Synthesis and Guideline Development in Reproductive Health Review of the Available Evidence on Taxanes (Paclitaxel and Docetaxel) for Breast Cancer. Modena, Italy. 2010.
    1. Liu J, Wang S, Zhang Y, et al. Traditional Chinese medicine and cancer: history, present situation, and development. Thorac Cancer 2015;6:561–9..
    1. Lin HS. Guidelines of Diagnosis and Therapy in Oncology With Traditional Chinese Medicine. Beijing: People's Medical Publishing House; 2014.
    1. Wang Z, Qi F, Cui Y, et al. An update on Chinese herbal medicines as adjuvant treatment of anticancer therapeutics. Biosci Trends 2018;12:220–39..
    1. Lam W, Jiang Z, Guan F, et al. PHY906(KD018), an adjuvant based on a 1800-year-old Chinese medicine, enhanced the anti-tumor activity of Sorafenib by changing the tumor microenvironment. Sci Rep 2015;5:9384.
    1. Liu S, He X, Man VH, et al. New application of in silico methods in identifying mechanisms of action and key components of anti-cancer herbal formulation YIV-906 (PHY906). Phys Chem Chem Phys 2019;21:23501–13..
    1. Jeong JS, Ryu BH, Kim JS, et al. Bojungikki-tang for cancer-related fatigue: a pilot randomized clinical trial. Integr Cancer Ther 2010;9:331–8..
    1. Cheon C, Kang S, Ko Y, et al. Sipjeondaebo-tang in patients with breast cancer with fatigue: a protocol for a pilot, randomised, double-blind, placebo-controlled, cross-over trial. BMJ Open 2018;8:e021242.
    1. Kong M, Hwang DS, Lee JY, et al. The Efficacy and Safety of Jaungo, a traditional medicinal ointment, in preventing radiation dermatitis in patients with breast cancer: a prospective, single-blinded, randomized pilot study. Evid Based Complement Alternat Med 2016;2016:9481413.
    1. Cheon C, Yoo JE, Yoo HS, et al. Efficacy and safety of Sipjeondaebo-Tang for anorexia in patients with cancer: a pilot, randomized, double-blind, placebo-controlled trial. Evid Based Complement Alternat Med 2017;2017:8780325.
    1. Lee JY, Oh HK, Ryu HS, et al. Efficacy and safety of the traditional herbal medicine, Gamiguibi-Tang, in patients with cancer-related sleep disturbance: a prospective, randomized, wait-list-controlled, pilot study. Integr Cancer Ther 2018;17:524–30..
    1. Cheon C, Kang S, Ko Y, et al. Maekmoondong-tang in treatment of postoperative cough in patients with lung cancer: study protocol for a randomized, double-blind, placebo-controlled, multicenter trial. Medicine (Baltimore) 2018;97:e11541.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅