Clinical trial NCT01451853: SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
Official title: Safety and Efficacy Study of SPI-1005 for Prevention of Chemotherapy Induced Hearing Loss
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lung Cancer
Head and Neck Cancer
Hearing Loss
Ototoxicity
Tinnitus
Neuropathy
Keywords: Lung Cancer
Head and Neck Cancer
Hearing Loss
Ototoxicity
Tinnitus
Deafness
SPI-1005
Cisplatin
Carboplatin
Ebselen
Lead sponsor: Sound Pharmaceuticals, Incorporated
Sponsor class: INDUSTRY
Collaborators: name: VA Puget Sound Health Care System
First posted: 2011-10-14
Enrollment: 80
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: 12 months
Secondary outcomes:
measure: Reduction of hearing loss incidence and severity
timeFrame: From baseline through 1 month after last chemotherapy cycle
measure: Reduction of tinnitus incidence and severity.
timeFrame: From baseline through 1 month after last chemotherapy cycle
Other outcomes:
Locations:
city: Seattle
country: United States
facility: VA Puget Sound Health Care
state: Washington
Study officials:
affiliation: Sound Pharmaceuticals, Inc.
name: Jonathan Kil, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Rybak LP, Somani S. Ototoxicity. Amelioration by protective agents. Ann N Y Acad Sci. 1999 Nov 28;884:143-51.
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. doi: 10.1016/j.heares.2004.08.002.
citation: 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.
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. doi: 10.1200/JCO.2006.07.9723.
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.
citation: 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.
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