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

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01451853
• Other study ID #: SPI-3005-201
• Status: Not yet recruiting
• Phase: Phase 2
• First received: October 7, 2011
• Last updated: September 21, 2017
• Start date: January 15, 2018
• Est. completion date: September 23, 2019

Study information

• Verified date: September 2017
• Source: Sound Pharmaceuticals, Incorporated
• Contact: Eric Lynch, PhD
• Phone: (206) 634-2559
• Email: elynch[@]soundpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: September 23, 2019
• Est. primary completion date: June 26, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Deafness
• Head and Neck Cancer
• Head and Neck Neoplasms
• Hearing Loss
• Lung Cancer
• Neuropathy
• Ototoxicity
• Tinnitus

Intervention

Drug:
• 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
• SPI-1005 Middle Dose
Oral capsules, 400 mg ebselen, twice daily, 3 days for each cycle of chemotherapy
• SPI-1005 High Dose
Oral capsules, 600 mg ebselen, twice daily, 3 days for each cycle of chemotherapy
• Placebo
Oral capsules, 0 mg ebselen, twice daily, 3 days for each cycle of chemotherapy

Locations

Country	Name	City	State
United States	VA Puget Sound Health Care	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Sound Pharmaceuticals, Incorporated	VA Puget Sound Health Care System

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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

Rybak LP, Whitworth C, Somani S. Application of antioxidants and other agents to prevent cisplatin ototoxicity. Laryngoscope. 1999 Nov;109(11):1740-4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events		12 months
Secondary	Reduction of hearing loss incidence and severity		From baseline through 1 month after last chemotherapy cycle
Secondary	Reduction of tinnitus incidence and severity.		From baseline through 1 month after last chemotherapy cycle