NCT02423811

To Study the Effect of Fursultiamine in Esophageal Squamous Cell Carcinoma Patients Who Receive Concurrent Chemoradiotherapy

Completed Phase 2 Last updated 11 March 2019

What this trial tests

Phase 2 trial testing Fursultiamine in Cancer Stem Cell in 20 participants. Completed in 1 December 2017.

Timeline

1 April 2015

Primary endpoint
1 December 2017

1 December 2017

Quick facts

Lead sponsor	National Cheng-Kung University Hospital
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	20
Start date	1 April 2015
Primary completion	1 December 2017
Estimated completion	1 December 2017
Sites	1 location across Taiwan

Drugs / interventions tested

• Fursultiamine (FURSULTIAMINE) — full drug profile →

Conditions studied

• Cancer Stem Cell — all drugs for Cancer Stem Cell →

Sponsor

National Cheng-Kung University Hospital

Who can join

Adults 20 to 75, any sex, with Cancer Stem Cell. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Progression-free survival
  Time frame: 5 year

Sponsor's own description

Esophageal cancer is a common and fatal malignancy. It is the eighth most common incident cancer and the sixth leading cause of cancer death in the world. In Taiwan, esophageal cancer was newly diagnosed in 2199 patients and was the cause of 1507 deaths in 2011. Squamous cell carcinoma is the predominant histological tumor type, accounting for about 90% of the cases. Esophageal squamous cell carcinoma (ESCC) is an aggressive disease, characterized with extensive local growth and frequent metastases. Concurrent chemoradiotherapy (CCRT) with or without surgery is the treatment option for locally advanced ESCC. Further, target therapy is used in conjunction with CCRT and surgery in ESCC since several years ago. However, the therapeutic outcomes are not satisfactory due to the emergence of chemo-radioresistance. It is imperative to investigate new biomarkers and to find novel treatment targets in ESCC.

A small population of tumor-initiating cells or cancer stem cells (CSCs) possess some biological functions like normal stem cells, including self-renewal, asymmetric cell division, slowly proliferation rate and drug-resistance. CSCs from many primary tumors and cell lines express specific stem cell markers, including Oct4, Sox2, Nanog, CD133 (promimin-1), Nestin, CD44 ,CD24, ALDH (Aldehyde dehydrogenase) and c-Kit. There are many evidences that CSCs are responsible for tumor initiation, progression and metastasis. CSCs are also believed to have important roles in cancer recurrence due to their resistance to anti-cancer drugs and radiation. CSCs express high levels of ATP-binding cassette (ABC) transporters. ABC transporter can pump cytotoxic drugs out of cells and is one important mechanism of multidrug resistance in CSCs. In addition, CSCs have high reactive oxygen species (ROS) scavenger expression to remove ROS produced from irradiation therapy.

Fursultiamine (also known as thiamine tetrahydrofurfuryl disulfide, TTFD) is a derivative of vitamin B and currently used for nutrition supplement. The investigators have identified that Fursultiamine suppressed OCT-4, SOX-2, NANOG expression and decreased ABCB1 and ABCG2 in tumor sphere of ESCC cell lines. In this project, the investigators will conduct a prospective phase II study to investigate the effect of Fursultiamine combined with CCRT in ESCC patients. Stem cell markers in clinical specimens collected before and after CCRT will be evaluated.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cancer stem cells: advances in knowledge and implications for cancer therapy.
   Chu X, Tian W, Ning J, Xiao G, et al · · 2024 · cited 311× · PMID 38965243 · DOI 10.1038/s41392-024-01851-y
2. Tumorsphere as an effective in vitro platform for screening anti-cancer stem cell drugs.
   Lee CH, Yu CC, Wang BY, Chang WW. · · 2016 · cited 128× · PMID 26527320 · DOI 10.18632/oncotarget.6261
3. Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review.
   Dzobo K, Senthebane DA, Ganz C, Thomford NE, et al · · 2020 · cited 86× · PMID 32823711 · DOI 10.3390/cells9081896
4. Drug resistance in cancer therapy: the Pandora's Box of cancer stem cells.
   Rezayatmand H, Razmkhah M, Razeghian-Jahromi I. · · 2022 · cited 82× · PMID 35505363 · DOI 10.1186/s13287-022-02856-6
5. Dietary Phytochemicals Targeting Cancer Stem Cells.
   Liskova A, Kubatka P, Samec M, Zubor P, et al · · 2019 · cited 70× · PMID 30836718 · DOI 10.3390/molecules24050899
6. Cancer Stem Cells: Powerful Targets to Improve Current Anticancer Therapeutics.
   Bighetti-Trevisan RL, Sousa LO, Castilho RM, Almeida LO. · · 2019 · cited 44× · PMID 31781251 · DOI 10.1155/2019/9618065
7. Transcription Factors: The Fulcrum Between Cell Development and Carcinogenesis.
   Islam Z, Ali AM, Naik A, Eldaw M, et al · · 2021 · cited 38× · PMID 34195082 · DOI 10.3389/fonc.2021.681377
8. Cancer stem cells: landscape, challenges and emerging therapeutic innovations.
   Lee H, Kim B, Park J, Park S, et al · · 2025 · cited 37× · PMID 40759634 · DOI 10.1038/s41392-025-02360-2