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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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.

Conditions
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Carcinoma, Non-small Cell Lung

Intervention / Treatment
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* Drug: ethaselen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental<br>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<br>* 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<br>* Other names: BBSKE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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. | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, thioredoxin reductase