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

NCT ID: NCT01451853

Last Updated: 2017-09-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-15

Study Completion Date

2019-09-23

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.

Conditions

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Lung Cancer Head and Neck Cancer Hearing Loss Ototoxicity Tinnitus Neuropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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SPI-1005 Low Dose

200 mg SPI-1005, capsule, po, bid, x3d surrounding each cycle of chemotherapy

Group Type ACTIVE_COMPARATOR

SPI-1005 Low Dose

Intervention Type DRUG

Oral capsules, 200 mg ebselen, twice daily, 3 days for each cycle of chemotherapy

Arms: Low Dose

Other Names:

200 mg Ebselen

SPI-1005 Middle Dose

400 mg SPI-1005, capsule, po, bid, x3d surrounding each cycle of chemotherapy

Group Type ACTIVE_COMPARATOR

SPI-1005 Middle Dose

Intervention Type DRUG

Oral capsules, 400 mg ebselen, twice daily, 3 days for each cycle of chemotherapy

SPI-1005 High Dose

600 mg SPI-1005, capsule, po, bid, x3d surrounding each cycle of chemotherapy

Group Type ACTIVE_COMPARATOR

SPI-1005 High Dose

Intervention Type DRUG

Oral capsules, 600 mg ebselen, twice daily, 3 days for each cycle of chemotherapy

Placebo

0 mg SPI-1005, capsule, po, bid, x3d surrounding each cycle of chemotherapy

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Oral capsules, 0 mg ebselen, twice daily, 3 days for each cycle of chemotherapy

Interventions

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SPI-1005 Low Dose

Oral capsules, 200 mg ebselen, twice daily, 3 days for each cycle of chemotherapy

Arms: Low Dose

Other Names:

200 mg Ebselen

Intervention Type DRUG

SPI-1005 Middle Dose

Oral capsules, 400 mg ebselen, twice daily, 3 days for each cycle of chemotherapy

Intervention Type DRUG

SPI-1005 High Dose

Oral capsules, 600 mg ebselen, twice daily, 3 days for each cycle of chemotherapy

Intervention Type DRUG

Placebo

Oral capsules, 0 mg ebselen, twice daily, 3 days for each cycle of chemotherapy

Intervention Type DRUG

Other Intervention Names

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200 mg Ebselen 400 mg Ebselen 600 mg Ebselen 0 mg Ebselen

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
Minimum Eligible Age

19 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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VA Puget Sound Health Care System

FED

Sponsor Role collaborator

Sound Pharmaceuticals, Incorporated

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jonathan Kil, MD

Role: STUDY_DIRECTOR

Sound Pharmaceuticals, Inc.

Locations

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VA Puget Sound Health Care

Seattle, Washington, United States

Site Status

Countries

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United States

Central Contacts

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Eric Lynch, PhD

Role: CONTACT

(206) 634-2559

Facility Contacts

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Tony S. Quang, M.D.

Role: primary

206-768-5356

References

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Rybak LP, Whitworth C, Somani S. Application of antioxidants and other agents to prevent cisplatin ototoxicity. Laryngoscope. 1999 Nov;109(11):1740-4. doi: 10.1097/00005537-199911000-00003.

Reference Type BACKGROUND
PMID: 10569399 (View on PubMed)

Rybak LP, Somani S. Ototoxicity. Amelioration by protective agents. Ann N Y Acad Sci. 1999 Nov 28;884:143-51.

Reference Type BACKGROUND
PMID: 10842591 (View on PubMed)

Lynch ED, Gu R, Pierce C, Kil J. Reduction of acute cisplatin ototoxicity and nephrotoxicity in rats by oral administration of allopurinol and ebselen. Hear Res. 2005 Mar;201(1-2):81-9. doi: 10.1016/j.heares.2004.08.002.

Reference Type BACKGROUND
PMID: 15721563 (View on PubMed)

Lynch ED, Gu R, Pierce C, Kil J. Combined oral delivery of ebselen and allopurinol reduces multiple cisplatin toxicities in rat breast and ovarian cancer models while enhancing anti-tumor activity. Anticancer Drugs. 2005 Jun;16(5):569-79. doi: 10.1097/00001813-200506000-00013.

Reference Type BACKGROUND
PMID: 15846123 (View on PubMed)

Knight KR, Kraemer DF, Winter C, Neuwelt EA. Early changes in auditory function as a result of platinum chemotherapy: use of extended high-frequency audiometry and evoked distortion product otoacoustic emissions. J Clin Oncol. 2007 Apr 1;25(10):1190-5. doi: 10.1200/JCO.2006.07.9723.

Reference Type BACKGROUND
PMID: 17401008 (View on PubMed)

Reavis KM, Phillips DS, Fausti SA, Gordon JS, Helt WJ, Wilmington D, Bratt GW, Konrad-Martin D. Factors affecting sensitivity of distortion-product otoacoustic emissions to ototoxic hearing loss. Ear Hear. 2008 Dec;29(6):875-93. doi: 10.1097/AUD.0b013e318181ad99.

Reference Type BACKGROUND
PMID: 18753950 (View on PubMed)

Kim SJ, Park C, Han AL, Youn MJ, Lee JH, Kim Y, Kim ES, Kim HJ, Kim JK, Lee HK, Chung SY, So H, Park R. Ebselen attenuates cisplatin-induced ROS generation through Nrf2 activation in auditory cells. Hear Res. 2009 May;251(1-2):70-82. doi: 10.1016/j.heares.2009.03.003. Epub 2009 Mar 13.

Reference Type BACKGROUND
PMID: 19286452 (View on PubMed)

Lynch E, Kil J. Development of Ebselen, a Glutathione Peroxidase Mimic, for the Prevention and Treatment of Noise-Induced Hearing Loss. Semin Hear 2009; 30(1): 047-055

Reference Type BACKGROUND

Other Identifiers

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SPI-3005-201

Identifier Type: -

Identifier Source: org_study_id