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

Carcinoma, Non-small Cell Lung Clinical Trial

Official title:

Phase 1c Single Arm Study of Thioredoxin Reductase Inhibitor Ethaselen, for the Treatment of Thioredoxin Reductase High Expressed Advanced Non-small Cell Lung Cancers Who Have Received More Than Two Lines Standard Treatment.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02166242
• Other study ID #: BBSKE001
• Status: Completed
• Phase: Phase 1
• Start date: June 1, 2014
• Est. completion date: December 1, 2021

Study information

• Verified date: March 2022
• Source: Hunan Province Tumor Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This phase 1c study will include 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, primary endpoint of this study is 6 week disease control rate(DCR, CR+PR+SD), secondary endpoints include progression free survival(PFS), overall survival(OS), quality of life(QOL) and drug safety.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 1, 2021
• Est. primary completion date: December 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• advanced non-small cell lung cancer, stage IIIB/IV who had received more than 2 standard treatment scheme

• 18-75 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Carcinoma, Non-small Cell Lung
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• ethaselen
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

Locations

Country	Name	City	State
China	Hunan province tumor hospital	Changsha	Hunan

Sponsors (1)

Lead Sponsor	Collaborator
Hunan Province Tumor Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2005 Jun 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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. Up to 30 weeks after the study was finished.	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.
Secondary	overall survival	the first time investigator evaluate OS will be at the sixth week since the study begin, the second time investigator evaluate OS will be at the 12th week, the next time will be at the 18th week. Up to 30 weeks after the study was finished.	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.
Secondary	safety of drug	any SAE should be recorded and reported to SFDA within 1 day during ethaselen treatment, after treatment drug associated safety will be in 6 weeks.	safety of drug will be recorded during treatment, up to 6 weeks after treatment