GASC1 Inhibitor Caffeic Acid for Squamous Esophageal Cell Cancer (ESCC)

NCT ID: NCT04648917

Last Updated: 2020-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-01

Study Completion Date

2022-05-01

Brief Summary

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Caffeic acid can target inhibit GASC1 (gene amplified in squamous cell carcinoma 1, also known as KDM4C and JMJD2C) expression and GASC1 is confirmed to be a new oncogene in several cancers including esophageal cancer. This study aims to investigate the efficiency and safety of coffeic acid in chinese advanced esophageal squamous cell cancer (ESCC).

Detailed Description

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Background: More than half of global esophageal cancer cases came from China.80 percentage patients were diagnosed with advanced disease and suffered from the poor outcome.With the development of target therapy among cancers,the overall survival and life quality of patients has been continuous improved recently.However,there had little reports focusing on target therapy in esophageal cancer . Caffeic acid as an ordinary drug is used for thrombocytopenia when patient received chemotherapy. Newly studies shown caffeic acid can target inhibit GASC1 expression, and GASC1 is confirmed to be a new oncogene in esophageal cancer.

Aim: to investigate the efficiency and safety of caffeic acid in chinese advanced esophageal squamous cell cancer.

Methods: 80 advanced ESCC patients who failed to the chemotherapy or chemoradiotherapy (1 or 2 line) will be randomized to two arms: arm A and arm B. In arm A, 40 patients will receive coffeic acid treatment: 100-200mg, tid, po, 2 weeks treated then 1 week black interval(weight \>50kg, 200mg per time, weight \< or =50kg, 100mg per time; in arm B, 40 patients will receive the placebo tablets. 1 years follow-up for all patients in this trial. Patients in both arms can receive any other ways of anti cancer therapy in the same time.

Primary endpoints: OS; Second endpoints: PFS

Conditions

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Esophagus Cancer, Stage III

Keywords

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esophageal cancer caffeic acid

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

1:1 Randomized grouping
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Arm A

In Arm A: 40 patients will receive coffeic acid treatment: 100-200mg, tid, po, 2 weeks treated then 1 week black interval (weight \>50kg, 200mg per time, weight \< or =50kg, 100mg per time)

Group Type EXPERIMENTAL

Caffeic acid

Intervention Type DRUG

40 patients will receive coffeic acid treatment: 100-200mg, tid, po, 2 weeks treated then 1 week black interval(weight \>50kg, 200mg per time, weight \< or =50kg, 100mg per time)

Arm B

In Arm B: 40 patients will receive the placebo tablets: 100-200mg, tid, po, 2 weeks treated then 1 week black interval.

Group Type PLACEBO_COMPARATOR

Caffeic acid

Intervention Type DRUG

40 patients will receive coffeic acid treatment: 100-200mg, tid, po, 2 weeks treated then 1 week black interval(weight \>50kg, 200mg per time, weight \< or =50kg, 100mg per time)

Interventions

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Caffeic acid

40 patients will receive coffeic acid treatment: 100-200mg, tid, po, 2 weeks treated then 1 week black interval(weight \>50kg, 200mg per time, weight \< or =50kg, 100mg per time)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Chinese
2. esophageal squamous cell cancer
3. stage IV or recurrence disease
4. chemotherapy, or radiotherapy, or palliative care is going on

Exclusion Criteria

1. PS (performance status): ≥ 3
2. severe hepatic and renal dysfunction
3. hypercoagulability
4. thrombocytosis
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The First Affiliated Hospital of Henan University of Science and Technology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Shegan Gao, Ph.D

Role: STUDY_CHAIR

The Clinical Medical College, The First Affiliated Hospital of Henan Science and Technology

Locations

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Anyang Tumor Hospital

Anyang, Henan, China

Site Status RECRUITING

The Clinical Medical College, The First Affiliated Hospital of Henan University of Science and Technology

Luoyang, Henan, China

Site Status RECRUITING

Nanyang Central Hospital

Nanyang, Henan, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Shegan Gao, Ph.D

Role: CONTACT

Phone: +86 18638859977

Email: [email protected]

Ruinuo Jia, Ph.D

Role: CONTACT

Phone: +86 18537950766

Email: [email protected]

Facility Contacts

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Fuyou Zhou, MD,PhD

Role: primary

Shegan Gao, PhD

Role: primary

Ruinuo Jia, MD

Role: backup

Lixin Wan, MD

Role: primary

References

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Pedersen MT, Kooistra SM, Radzisheuskaya A, Laugesen A, Johansen JV, Hayward DG, Nilsson J, Agger K, Helin K. Continual removal of H3K9 promoter methylation by Jmjd2 demethylases is vital for ESC self-renewal and early development. EMBO J. 2016 Jul 15;35(14):1550-64. doi: 10.15252/embj.201593317. Epub 2016 Jun 6.

Reference Type RESULT
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Movassaghian S, Xie Y, Hildebrandt C, Rosati R, Li Y, Kim NH, Conti DS, da Rocha SR, Yang ZQ, Merkel OM. Post-Transcriptional Regulation of the GASC1 Oncogene with Active Tumor-Targeted siRNA-Nanoparticles. Mol Pharm. 2016 Aug 1;13(8):2605-21. doi: 10.1021/acs.molpharmaceut.5b00948. Epub 2016 Jun 27.

Reference Type RESULT
PMID: 27223606 (View on PubMed)

Sudo G, Kagawa T, Kokubu Y, Inazawa J, Taga T. Increase in GFAP-positive astrocytes in histone demethylase GASC1/KDM4C/JMJD2C hypomorphic mutant mice. Genes Cells. 2016 Mar;21(3):218-25. doi: 10.1111/gtc.12331. Epub 2016 Jan 25.

Reference Type RESULT
PMID: 26805559 (View on PubMed)

Jia R, Yang L, Yuan X, Kong J, Liu Y, Yin W, Gao S, Zhang Y. GASC1 Promotes Stemness of Esophageal Squamous Cell Carcinoma via NOTCH1 Promoter Demethylation. J Oncol. 2019 Mar 26;2019:1621054. doi: 10.1155/2019/1621054. eCollection 2019.

Reference Type RESULT
PMID: 31031809 (View on PubMed)

Uimonen K, Merikallio H, Paakko P, Harju T, Mannermaa A, Palvimo J, Kosma VM, Soini Y. GASC1 expression in lung carcinoma is associated with smoking and prognosis of squamous cell carcinoma. Histol Histopathol. 2014 Jun;29(6):797-804. doi: 10.14670/HH-29.797. Epub 2013 Dec 27.

Reference Type RESULT
PMID: 24371038 (View on PubMed)

Sun LL, Holowatyj A, Xu XE, Wu JY, Wu ZY, Shen JH, Wang SH, Li EM, Yang ZQ, Xu LY. Histone demethylase GASC1, a potential prognostic and predictive marker in esophageal squamous cell carcinoma. Am J Cancer Res. 2013 Nov 1;3(5):509-17. eCollection 2013.

Reference Type RESULT
PMID: 24224128 (View on PubMed)

Berdel B, Nieminen K, Soini Y, Tengstrom M, Malinen M, Kosma VM, Palvimo JJ, Mannermaa A. Histone demethylase GASC1--a potential prognostic and predictive marker in invasive breast cancer. BMC Cancer. 2012 Nov 14;12:516. doi: 10.1186/1471-2407-12-516.

Reference Type RESULT
PMID: 23148692 (View on PubMed)

Jia R, Mi Y, Yuan X, Kong D, Li W, Li R, Wang B, Zhu Y, Kong J, Ma Z, Li N, Mi Q, Gao S. GASC1-Adapted Neoadjuvant Chemotherapy for Resectable Esophageal Squamous Cell Carcinoma: A Prospective Clinical Biomarker Trial. J Oncol. 2020 Jan 30;2020:1607860. doi: 10.1155/2020/1607860. eCollection 2020.

Reference Type RESULT
PMID: 32411232 (View on PubMed)

Yang ZQ, Imoto I, Fukuda Y, Pimkhaokham A, Shimada Y, Imamura M, Sugano S, Nakamura Y, Inazawa J. Identification of a novel gene, GASC1, within an amplicon at 9p23-24 frequently detected in esophageal cancer cell lines. Cancer Res. 2000 Sep 1;60(17):4735-9.

Reference Type RESULT
PMID: 10987278 (View on PubMed)

Cederblad L, Thunberg U, Engstrom M, Castro J, Rutqvist LE, Laytragoon-Lewin N. The combined effects of single-nucleotide polymorphisms, tobacco products, and ethanol on normal resting blood mononuclear cells. Nicotine Tob Res. 2013 May;15(5):890-5. doi: 10.1093/ntr/nts207. Epub 2012 Oct 4.

Reference Type RESULT
PMID: 23042982 (View on PubMed)

Yuan X, Kong J, Ma Z, Li N, Jia R, Liu Y, Zhou F, Zhan Q, Liu G, Gao S. KDM4C, a H3K9me3 Histone Demethylase, is Involved in the Maintenance of Human ESCC-Initiating Cells by Epigenetically Enhancing SOX2 Expression. Neoplasia. 2016 Oct;18(10):594-609. doi: 10.1016/j.neo.2016.08.005. Epub 2016 Sep 19.

Reference Type RESULT
PMID: 27742014 (View on PubMed)

Other Identifiers

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GiCAEC-LY002

Identifier Type: -

Identifier Source: org_study_id