Ethaselen for the Treatment of Thioredoxin Reductase High Expression Advanced Non-small Cell Lung Cancers

NCT02166242 | Completed Phase 1

• 1 other identifier: BBSKE001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Thioredoxin reductase plays an critical role in lung cancer patients, in vitro study showed that, ethaselen, specific inhibitor of thioredoxin reductase, could inhibit lung cancer cell growth and induce apoptosis. In China, phase 1 clinical trials of ethaselen showed that 1200 mg dose ethaselen could be well tolerated, in pre-clinical study we found that, approximately 50% non-small cell lung cancers harbored high thioredoxin reductase expression(IHC result ++ or +++), phase 1a/b of ethaselen had finished in 2008, the result showed that 1200mg ethaselen per day was safety and tolerated by Chinese malignant tumor patients.In pre-clinical research, our group found that, elevated of thioredoxin reductase activity was associated with the expression of thioredoxin reductase tested by immunohistochemistry, which means high expression of this enzyme may be a favourite predicted factor of ethaselen, the specific inhibitor of thioredoxin reductase.

Conditions

Carcinoma, Non-small Cell Lung

Keywords

non-small cell lung cancer; thioredoxin reductase

Outcome Measures

Primary Outcomes (1)

• 6 week disease control rate

  disease control rate will be measured within 6 weeks after patients received ethaselen treatment

  within 6 weeks after patients received ethaselen treatment

Secondary Outcomes (3)

• progression free survival

  the first time investigator evaluate PFS will be at the sixth week since the study begin, the second time investigator evaluate PFS will be at the 12th week, the next time will be at the 18th week.

• overall survival

  the first time investigator evaluate OS will be at the sixth week since the study begin, the second time investigator evaluate PFS will be at the 12th week, the next time will be at the 18th week. Up to 30 weeks after the study was finished.

• safety of drug

  safety of drug will be recorded during treatment, up to 6 weeks after treatment

Study Arms (1)

experimental

EXPERIMENTAL

patients pathologic diagnosis advanced non-small cell lung cancer who had received more than two lines standard treatment, according to NCCN Non-small cell lung cancer guideline, there were no standard treatment scheme for these patients. Approximately 40 patients will be included in the study, patients will received oral ethaselen dispersible tablet, 600 mg bid dose, patients may quit the study whenever they would like or investigator evaluate that progression disease has developed, or any grade of SAE developed during the study.

Drug: ethaselen

Interventions

ethaselen DRUG

ethaselen is a specific thioredoxin reductase inhibitor, which has finished phase 1a study in China, phase 1 study of ethaselen showed that 600 mg ethaselen bid could be well tolerated

Also known as: BBSKE

experimental

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• advanced non-small cell lung cancer, stage IIIB/IV who had received more than 2 standard treatment scheme
• years old, anticipate overall survival more than 3 months, ECOG 0-2
• within 4 weeks, not receive chemotherapy, radiotherapy or surgery
• HB≥90g/L； ANC ≥1.5×109/L；PLT ≥80×109/L
• EGFR/ALK mutation negative
• immunohistochemistry test of cancer tissue showed ++ or +++ of thioredoxin reductase
• brain metastasis without symptoms

You may not qualify if:

• according to NCCN non-small cell lung cancer guidelines (2014 v3), there were standard treatment scheme for the patients
• pregnancy or breast-feeding women
• any serious disease which could not be controled
• urine protein≥++, or 24h urine protein\>1g
• received any anti-cancer treatment within 4 weeks

Sponsors & Collaborators

• Hunan Province Tumor Hospital: lead

Study Sites (1)

Hunan province tumor hospital

Changsha, Hunan, China

Location

Related Publications (6)

• Wang L, Yang Z, Fu J, Yin H, Xiong K, Tan Q, Jin H, Li J, Wang T, Tang W, Yin J, Cai G, Liu M, Kehr S, Becker K, Zeng H. Ethaselen: a potent mammalian thioredoxin reductase 1 inhibitor and novel organoselenium anticancer agent. Free Radic Biol Med. 2012 Mar 1;52(5):898-908. doi: 10.1016/j.freeradbiomed.2011.11.034. Epub 2011 Dec 21.

  PMID: 22210352 BACKGROUND

• Wang L, Fu JN, Wang JY, Jin CJ, Ren XY, Tan Q, Li J, Yin HW, Xiong K, Wang TY, Liu XM, Zeng HH. Selenium-containing thioredoxin reductase inhibitor ethaselen sensitizes non-small cell lung cancer to radiotherapy. Anticancer Drugs. 2011 Sep;22(8):732-40. doi: 10.1097/CAD.0b013e32834618bc.

  PMID: 21562407 BACKGROUND

• Poerschke RL, Moos PJ. Thioredoxin reductase 1 knockdown enhances selenazolidine cytotoxicity in human lung cancer cells via mitochondrial dysfunction. Biochem Pharmacol. 2011 Jan 15;81(2):211-21. doi: 10.1016/j.bcp.2010.09.024. Epub 2010 Oct 12.

  PMID: 20920480 BACKGROUND

• Zhao F, Yan J, Deng S, Lan L, He F, Kuang B, Zeng H. A thioredoxin reductase inhibitor induces growth inhibition and apoptosis in five cultured human carcinoma cell lines. Cancer Lett. 2006 May 8;236(1):46-53. doi: 10.1016/j.canlet.2005.05.010. Epub 2005 Jun 27.

  PMID: 15982805 BACKGROUND

• Fu JN, Li J, Tan Q, Yin HW, Xiong K, Wang TY, Ren XY, Zeng HH. Thioredoxin reductase inhibitor ethaselen increases the drug sensitivity of the colon cancer cell line LoVo towards cisplatin via regulation of G1 phase and reversal of G2/M phase arrest. Invest New Drugs. 2011 Aug;29(4):627-36. doi: 10.1007/s10637-010-9401-y. Epub 2010 Mar 2.

  PMID: 20195699 BACKGROUND

• Tan Q, Li J, Yin HW, Wang LH, Tang WC, Zhao F, Liu XM, Zeng HH. Augmented antitumor effects of combination therapy of cisplatin with ethaselen as a novel thioredoxin reductase inhibitor on human A549 cell in vivo. Invest New Drugs. 2010 Jun;28(3):205-15. doi: 10.1007/s10637-009-9235-7. Epub 2009 Mar 7.

  PMID: 19271154 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

(1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone))ethane

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Nong Yang, MD

  Hunan Province Tumor Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of department of medical oncology, lung cancer and gastrointestinal cancer unit

Study Record Dates

• First Submitted: June 1, 2014
• First Posted: June 18, 2014
• Study Start: June 1, 2014
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2021
• Last Updated: March 16, 2022

Record last verified: 2022-03

Locations

CN (1)