SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss

Study Overview
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Brief Summary
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Chemotherapy treatment with platinum based agents is well noted to cause ototoxicity. It is the objective of this study to determine the safety and efficacy of SPI-1005 at three dose levels when delivered orally twice daily for 3 days, surrounding each cycle of platinum chemotherapy in head and neck or non-small cell lung cancer patients to prevent and treat chemotherapy induced hearing loss and tinnitus.

Detailed Description
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Chemotherapy treatment with the platinum containing chemotherapies (e.g. cisplatin, carboplatin) are well noted and studied for their ability to cause ototoxicity which includes hearing loss, tinnitus, vertigo, or dizziness. It is the objective of this study to determine the safety and efficacy of SPI-1005 at three dose levels when delivered orally twice daily for 3 days, surrounding each cycle of platinum chemotherapy for head and neck or non-small cell lung cancer patients to prevent and treat chemotherapy induced hearing loss and tinnitus. SPI-1005, a proprietary oral formulation of ebselen is a small molecule mimic and inducer of the enzyme Glutathione Peroxidase. GPx reduces reactive oxygen species (ROS) by reacting with glutathione. SPI-1005 has been shown to reduce cisplatin induced hearing threshold shift in animal studies.

Official Title
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Safety and Efficacy Study of SPI-1005 for Prevention of Chemotherapy Induced Hearing Loss

Conditions
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Lung Cancer, Head and Neck Cancer, Hearing Loss, Ototoxicity, Tinnitus, Neuropathy

Intervention / Treatment
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* Drug: SPI-1005 Low Dose
* Drug: SPI-1005 Middle Dose
* Drug: SPI-1005 High Dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male and female subjects, 19-80 years of age; Confirmed diagnosis of advanced head and neck cancer or advanced lung cancer Voluntarily consent to participate in the study Females of childbearing potential should either be sexually inactive (abstinent) for 14 days prior to screening and throughout the study or be using one of the following acceptable birth control methods: IUD in place for at least 3 months prior to study; Barrier method (condom or diaphragm) with spermicide for at least 14 days prior to screening through study completion; Stable hormonal contraceptive for at least 3 months prior to study through completion of study; Surgical sterilization (vasectomy) of partner at least 6 months prior to study. Females of non-childbearing potential should be surgically sterile (bilateral tubal ligation with surgery at least 6 months prior to study, hysterectomy, or bilateral oophorectomy at least 2 months prior to study). Exclusion Criteria: Subjects previously treated with chemotherapy, antibiotics, or diuretics known to cause hearing loss in the last 90 days History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, otologic, or psychiatric disease Presence of alcoholism or drug abuse Participation in another investigational drug or device clinical trial within 30 days prior to the study Female subjects who are pregnant or lactating

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SPI-1005 Low Dose<br>200 mg SPI-1005, capsule, po, bid, x3d surrounding each cycle of chemotherapy | Drug: SPI-1005 Low Dose<br>* Oral capsules, 200 mg ebselen, twice daily, 3 days for each cycle of chemotherapy Arms: Low Dose Other Names: 200 mg Ebselen<br>* Other names: 200 mg Ebselen;|
| Active Comparator: SPI-1005 Middle Dose<br>400 mg SPI-1005, capsule, po, bid, x3d surrounding each cycle of chemotherapy | Drug: SPI-1005 Middle Dose<br>* Oral capsules, 400 mg ebselen, twice daily, 3 days for each cycle of chemotherapy<br>* Other names: 400 mg Ebselen;|
| Active Comparator: SPI-1005 High Dose<br>600 mg SPI-1005, capsule, po, bid, x3d surrounding each cycle of chemotherapy | Drug: SPI-1005 High Dose<br>* Oral capsules, 600 mg ebselen, twice daily, 3 days for each cycle of chemotherapy<br>* Other names: 600 mg Ebselen;|
| Placebo Comparator: Placebo<br>0 mg SPI-1005, capsule, po, bid, x3d surrounding each cycle of chemotherapy | Drug: Placebo<br>* Oral capsules, 0 mg ebselen, twice daily, 3 days for each cycle of chemotherapy<br>* Other names: 0 mg Ebselen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of hearing loss incidence and severity |  | From baseline through 1 month after last chemotherapy cycle | 
| Reduction of tinnitus incidence and severity. |  | From baseline through 1 month after last chemotherapy cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Cancer, Head and Neck Cancer, Hearing Loss, Ototoxicity, Tinnitus, Deafness, SPI-1005, Cisplatin, Carboplatin, Ebselen