Phase 1b trial to investigate the prevention of hearing loss in cancer patients receiving cisplatin chemotherapy
Phase 1b Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Repeated Doses of DB-020 in Patients Receiving Cisplatin
Decibel Therapeutics Australia Pty Ltd
70 participants
Feb 28, 2020
Interventional
Conditions
Summary
Cisplatin is a medication anti-cancer chemotherapy that can cause damage to the inner ear of patients leading to hearing loss. A medication called DB-020 has been developed as a potential treatment for this hearing loss. The purpose of this study is to test how the body tolerates and processes DB-020 injected into the inner ear and make sure it is safe. Who is it for? You may be eligible for this study if you are aged at least 18 years old and are undergoing chemotherapy for cancer with a medication called cisplatin. Study details This study has two parts. In the first part, all participants will have ear injections. One of the ears will be treated with DB-020 and the other will be treated with a salt-based solution (a placebo). The concentration of DB-020 used and the ear that receives DB-020 will be determined by chance (like flipping a coin). Treatment involves an ear injection in line with cisplatin chemotherapy - every 3 or 4 weeks. In the second part, all participants will have ear injections of DB-020 at a concentration determined by the first part. Depending on the safety analysis from the data in Part A, participants will receive one ear with placebo and the other with DB-020, or DB-020 in both ears. As part of this study, all participants will provide blood samples; answer questionnaires and have hearing tests. It is hoped this research will provide some evidence that DB-020 can be used as a preventative treatment of hearing loss for patients receiving cisplatin treatment and provide the basis for further trials with this medication.
Eligibility
Inclusion Criteria14
- Ability to communicate with medical team and staff, willingness to participate in the study, willingness to give written informed consent, and willingness to comply with the study restrictions.
- Adults aged 18 to 75 years, inclusive, at the time of signing the informed consent form.
- Patients with cancer for whom treatment with IV cisplatin once every 21 or 28 days is indicated must meet all of the following criteria.
- a. Plan to receive a minimum cumulative dose of cisplatin of greater than or equal to 280 mg/m2 over at least three cycles (21-day or 28-day cycles) for treatment of cancer of any type.
- b. Concomitant use of other chemotherapy and radiation is permitted except investigational agents and/or radiation > 35 Gy 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. Acceptable barrier forms of contraception are condom and diaphragm. Acceptable forms of contraception for this study for female partner(s) of childbearing potential and premenopausal female patients are nonhormonal and hormonal intrauterine device (IUD), hormonal birth control pills, hormonal birth control patches, hormonal birth control injections (eg, Depo-Provera®), hormonal birth control implants, NuvaRing®, and/or spermicide. 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, will be eligible to participate in the study.
- Women of nonchildbearing potential are eligible for the study and are defined as 12 months with no menses prior to screening and a serum FSH >40 IU/L at Screening (ie, postmenopausal female patients), or surgically sterile female patients, eg, those having undergone total abdominal hysterectomy, bilateral oophorectomy, or bilateral tubal ligation at least 6 months prior to screening for study participation. Surgically sterile female patients may participate if they agree to use condoms with spermicide during the study and for
- days after the last study drug administration.
- Men who have undergone a vasectomy at least 6 months prior to Screening and who have a documented negative sperm count (eg, medical records or single semen specimen) after the procedure are not required to use contraception.
- Male patients must agree to refrain from sperm donation within 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 Criteria13
- 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, ontological surgery (excluding myringotomy tubes or simple tympanoplasty), sudden hearing loss, conductive hearing loss > 10 dB at 2 frequencies in either ear, Meniere’s disease, or autoimmune middle ear disease.
- Hearing loss greater than (not including) 35 dB HL averaged at 6 and 8 kHz in either ear.
- Asymmetry in hearing thresholds between left and right ear equal to or exceeding 20 dB at any single frequency or 10 dB at any 3 consecutive frequencies, up to and including 8 kHz.
- Previous radiation exposure > 35 Gy to all or part of the cochlea.
- Consumption of > 6 g of salicylate or > 5 g 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.
- History or presence of malignancy within the past 5 years other than a history of localized or surgical removal of focal basal cell skin cancer; cervical cancer in situ treated successfully in the past by local treatment (including but not limited to cryotherapy or laser therapy) or by hysterectomy, or malignancy for which the patient is receiving cisplatin therapy.
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Interventions
Brief name of intervention: Repeated intratympanic (IT) injections of sodium thiosulfate (STS) pentahydrate in patients receiving cisplatin. STS pentahydrate to be hereafter designated as DB-020. Repeated doses: IT injections will be administered once every 3 weeks or once every 4 weeks, according to the cisplatin dosing schedule, as close to cisplatin administration as possible, ideally after intravenous(IV) fluids for hydration have been started but within 3 hours prior to the patient receiving his/her cisplatin treatment. Eligible patients are those planned to receive a minimum cumulative dose of cisplatin of greater than or equal to 280 mg per m^2 over at least three cycles (21-day or 28-day cycles) for treatment of cancer of any type. Study Drug Administration: Patients will be randomized to receive blinded, bilateral, IT treatment where patients will receive DB-020 in one ear with placebo in the other. In Part B, patients may receive DB-020 in both ears. The administration of these injections, to be performed by a qualified otolaryngologist and is expected to take 1-2 min per injection. DB-020 for Injection, at either 12% or 25%, is provided as a single use vial containing a sterile viscous solution of DB-020 and sodium hyaluronate in sterile water. The placebo is provided as a single use vial containing a sterile viscous solution of sodium hyaluronate in 0.9% sodium chloride. The study will comprise 2 parts. Separate patients will participate in Parts A and B Part A: Eligible patients will be randomized to 12% or 25% dose levels of DB-020. Patients will be randomized to receive blinded, bilateral, IT treatment. Patients will receive DB-020 in one ear with placebo in the other. The ear to be injected with DB-020 throughout the treatment period will be randomly assigned and the contralateral ear will be injected with placebo. Part B: Patients will be randomized to a single dose level of DB-020, as selected from data collected in Part A. The output of the interim analysis of Part A will provide the information necessary to select the concentration for Part B. This analysis will incorporate key safety and efficacy data to ensure patient safety and opportunity for efficacy and will be used to select the most appropriate dose for Part B. If the prevention of ototoxicity as defined by American Speech-Language-Hearing Association (ASHA) criteria is observed in DB-020 treated ears in Part A, 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. This protocol uses a 1:1:1:1 central randomization without stratification variables. Each patient will be randomized to receive one of two dose strengths (12% or 25%) in Part A, and the ear to receive active IP vs. placebo is also randomly assigned.
Locations(5)
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ACTRN12620000182998