Study to Evaluate Safety and Efficacy of DB-020 to Protect Hearing in Patients Receiving Cisplatin for Cancer Treatment

Decibel Therapeutics22 enrolled

Overview

The purpose of this study is to evaluate whether DB-020 administered via an injection in the middle ear prevents hearing loss in participants who will receive high doses of cisplatin as part of their treatment for cancer.

Cisplatin is a widely used and effective chemotherapy in the treatment of adult and pediatric solid tumors, including bladder, testicular, head and neck, and lung cancers. Serious side effects of cisplatin treatment include ototoxicity. To date, no approved therapy to prevent or treat ototoxicity exists for people receiving cisplatin treatment, which remains the most common dose-limiting side effect associated with cisplatin administration. Participants who will be undergoing cancer treatment with high doses of cisplatin every 21 or 28 days will receive IT injection with one ear receiving DB-020 and one ear receiving placebo during each administration. The study will comprise 2 parts. In Part A, eligible participants will be randomized to one of two doses of DB-020. In Part B, participants will be treated with a single dose of DB-020, as selected from data collected in Part A. In both Parts A and B, the ear receiving DB-020 or placebo will be randomized. The choice of dose in Part B will depend on the data from Part A. If appropriate safety and efficacy is observed at either dose level, the Sponsor has the option of dosing at one of these concentrations either unilaterally (ie, with placebo administered in the contralateral ear) or bilaterally (ie, open-label DB-020 administered to both ears) in Part B.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

Conditions

Ototoxicity

Interventions

DB-020DRUG

Injectable sterile viscous solution of DB-020 and sodium hyaluronate in sterile water

PlaceboDRUG

Injectable sterile viscous solution of sodium hyaluronate in sodium chloride

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Ability to communicate with medical team and staff, willingness to participate in the study, give written informed consent, comply with the study restrictions * Adults aged 18 years, inclusive, or older * Treatment for cancer with Intervenous cisplatin once every 21 or 28 days * Plan to receive a minimum cumulative dose of cisplatin of ≥ 280 mg/m2 over at least three cycles * Concomitant use of other chemotherapy and radiation is permitted except investigational agents and/or radiation \> 35 Grays involving the cochlear area * Male patients, their female partner(s), and female patients of childbearing potential must agree to use 2 forms of contraception, 1 of which must be a barrier method, during the study and for 90 days after the last study drug administration. * Male and female patients who consider themselves abstinent, and who agree to remain abstinent during the study and for 90 days after the last study drug administration * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 * Anticipated survival \> 1 year * Normal or not clinically significant otoscopic findings in both ears * Patient has read, understood, and voluntarily signed the informed consent form. Exclusion Criteria: * Female or male patients with female partners who are pregnant, lactating, or planning to attempt to become pregnant during this study or within 90 days after last dose of study drug * Prior treatment with a cisplatin regimen * Signs of disturbed integrity of the tympanic membrane on otoscopy or tympanometry * History of congenital hearing loss * History of otological surgery (excluding myringotomy tubes or simple tympanoplasty) * History of sudden hearing loss * History of conductive hearing loss \> 10 decibels at 2 frequencies in either ear * Diagnosis of Meniere's disease * Diagnosis of autoimmune middle ear disease * Hearing loss greater than (not including) 45 decibels Hearing Loss averaged at 6 and 8 kilohertz in either ear * Asymmetry in hearing thresholds between left and right ear equal to or exceeding 20 decibels at any single frequency or 10 decibels at any 3 consecutive frequencies, up to and including 8 kilohertz * Previous radiation exposure \> 35 Grays to all or part of the cochlea * Consumption of \> 6 grams of salicylate or \> 5 grams of acetaminophen (paracetamol) per day for the past month, or aminoglycoside use in the past month * Use of any investigational drug or device within 30 days prior to the first dose of study medication (6 months for biologic therapies) or 5 half-lives of the investigational drug, if known, whichever time is longer * History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) and/or allergy to the excipients of the study medications * Presence of hepatitis C antibody with reflex hepatitis C virus (HCV) RNA testing (if anti-HCV is positive), hepatitis B surface antigen, or HIV antibodies 1 and 2

Locations (8)

University of Miami Health System

Miami, Florida, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Northwell Health Cancer Center

Lake Success, New York, United States

WVU Cancer Institute

Outcomes

Primary Outcomes

Number of patients with treatment-emergent Adverse Events (TEAEs) and/or abnormal changes from baseline in clinical laboratory abnormalities and/or vital signs and/or ECG assessments

To investigate the safety and tolerability of DB-020 when given intratympanically to patients receiving cisplatin chemotherapy treatment

Time frame: From screening/baseline (Day -28 to Day -2) or day of first dose of DB-020 (Cycle 1 Day 1) for up to 6 cycles (21 or 28 day cycles) through End of Treatment Visit (28 days after last dose of study drug), up to 196 Days after first dose of study drug

Secondary Outcomes

Incidence of Ototoxicity measured by American Speech-Language-Hearing Association (ASHA) criteria

Air conduction audiometry consists of a set of pure tones presented to the patient through small speakers in a headset, played at carrier frequencies ranging from 250 to 16,000 Hz. Pure tone thresholds are recorded for each frequency tested. Ototoxicity will be defined according to the American Speech-Language-Hearing Association (ASHA) criteria for significant ototoxic change. Significant ototoxic change must meet one of the following three criteria: (i) ≥20 dB decrease at any one test frequency, (ii) ≥10 dB decrease at any two adjacent frequencies, or (iii) loss of response at three consecutive frequencies where responses were previously obtained. The presence of ototoxicity will be calculated for each ear

Time frame: Baseline (Day -5 to Day -1) for up to 6 cycles (21 or 28 day cycles) through End of Treatment Visit (28 days after last dose of study drug), up to 196 Days after first dose of study drug

Changes from Baseline in Pure Tone Threshold Values compared to End of Treatment [Changes in Hearing]

Air conduction audiometry consists of a set of pure tones presented to the patient through small speakers in a headset, played at carrier frequencies ranging from 250 to 16,000 Hz. Pure tone thresholds are recorded for each frequency tested. Higher values indicate a greater degree of hearing impairment. Changes from baseline values will be calculated for each frequency and ear as the reported pure tone threshold value minus the baseline value. A negative change from baseline indicates hearing loss

Data from ClinicalTrials.gov

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