SENS-401 to Prevent the Ototoxicity induced by Cisplatin in Adult Subjects with a Neoplastic Disease
- Conditions
- Cisplatine induced hearing loss
- Interventions
- Drug: SENS-401 (R-Azasetron Besylate)
- Registration Number
- 2024-511713-38-00
- Lead Sponsor
- Sensorion
- Brief Summary
To evaluate the efficacy of SENS-401 given at the dose of 43.5 mg b.i.d. (bis in die) for up to 23 weeks to prevent the ototoxicity induced by cisplatin in subjects with a neoplastic disease, 4 weeks after the completion of the last cisplatin treatment.
- Detailed Description
This study is intended to evaluate the ability of SENS-401 to prevent the ototoxicity induced by cisplatin in subjects with a neoplastic disease. It is a multicenter, randomized, controlled, two-arm, open-label efficacy and safety study in adults with neoplastic disease requiring treatment with cisplatin as part of the chemotherapy protocol plan. Cisplatin treatment per chemotherapy protocol must be given at a cumulative dose high enough to significantly increase the iatrogenic likelihood of ototoxicity (unit cisplatin dose of at least 70 mg/m2 and cumulative cisplatin dose of at least 210 mg/m²). If all the eligibility criteria are met, subjects will be randomized to one of two study arms as follows:
* Study Arm A (control arm): Subjects receiving cisplatin-based chemotherapy without receiving SENS-401. This control arm will provide natural history data, particularly the incidence and the time to onset of hearing impairment due to ototoxicity.
* Study Arm B: Subjects receiving 43.5 mg of oral SENS-401 b.i.d for up to 23 weeks: 1 week prior to the initiation of the cisplatin treatment, during the whole duration of the chemotherapy treatment (estimated to last up to 18 weeks) and 4 weeks after stopping chemotherapy. This arm will provide data on the potential protective effects of SENS-401 on cisplatin induced ototoxicity.
All subjects will be followed up to 12 weeks after the completion of the cisplatin therapy.
Recruitment & Eligibility
- Status
- Ended
- Sex
- Not specified
- Target Recruitment
- 48
Age ≥ 18 years at the time of signing the ICF.
Capable of giving signed informed consent as described in Appendix 2 of this protocol, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
A female subject is eligible to participate if she is not pregnant (see Appendix 6), not breastfeeding, and ≥ 1 of the following conditions apply: • Not a woman of childbearing potential (WOCBP) as defined in Appendix 6. • A WOCBP who agrees to follow the contraceptive guidance in Appendix 6 for at least 30 days after the last dose of SENS-401 if cisplatin is not received or 6 months after the last dose of cisplatin.
A male subject must agree to use contraception and refrain from donating sperm as detailed in Appendix 6 of this protocol for at least 30 days after the last dose of SENS-401 if cisplatin is not received or 6 months after the last dose of cisplatin.
Neoplastic subject that, regardless of participation in this study, is planned to be treated with a chemotherapy that includes a dose of cisplatin of at least 70 mg/m2 per cycle and a cumulative dose of cisplatin of at least 210 mg/m2.
6b. Subjects with a PTA threshold of ≤ 30 dB at 500 Hz AND ≤ 40 dB at 1-2 kHz AND ≤ 60 dB at 4-6 kHz AND ≤ 80 dB at 8 kHz, in either both ears or one ear for a maximum of 30% of the subjects in each study arm.
In the opinion of the Investigator, a life expectancy of ≥ 6 months.
Inclusion Criterion 8 about COVID-19 has been removed from study protocol v4.0.
Any condition or past medical history that, in the opinion of the Investigator, may compromise the safety or compliance of the subject or would preclude the subject from successful completion of the study.
History of meningitis.
For a subject expected to receive radiotherapy during the course of the study, an anticipated risk of exposure of the auditory system (i.e. inner ear within the expected irradiation zone).
History of significant arrhythmia or conditions known to increase proarrhythmic risk (e.g. congestive heart failure, long QT syndrome, hypokalemia).
Significant clinically relevant electrocardiogram (ECG) abnormality that, in the opinion of the Investigator, precludes study eligibility.
Significant abnormal laboratory result, physical examination, vital signs, or ear-nose-throat (ENT) evaluation (otoscopy and immittance audiometry), in the opinion of the Investigator.
Neurological disorder including stroke, demyelinating disease, or brain stem or cerebellar dysfunction.
Moderate to severe renal impairment defined by a creatinine clearance ≤ 60 mL/min (calculated with the Cockcroft-Gault formula for subjects < 65 years old and with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation or with the Modification of Diet in Renal Disease (MDRD) equation for subjects ≥ 65 years old
Exclusion Criterion 17 about statins has been removed from study protocol v4.0.
Having received concomitant treatment known or suspected to induce an ototoxicity within 6 months prior to Screening (i.e. aminoglycosides, loop diuretics, quinine) and any other treatments listed in Appendix 5. Previous treatment with a platinum treatment should be considered as an exclusion criterion.
Treatment with any investigational agent within 4 weeks prior to screening or 5 half-lives of the investigational drug (whichever is longer).
Subject is the Investigator or anyone from his/her team directly involved in the conduct of the protocol.
20b. Known or suspected ongoing active infection of human immunodeficiency virus (HIV)
- Known hypersensitivity, allergy or intolerance to the study medication or any history of severe abnormal drug reaction.
Known hypersensitivity, allergy or intolerance to cisplatin or any history of severe abnormal drug reaction.
Receiving phenytoin at screening (as it is contraindicated with cisplatin).
Myelosuppressed at screening (as it is contraindicated with cisplatin).
Any condition or health state at screening contraindicating the use of rehydration solution before each cisplatin cycle if requested (as dehydration state is contraindicated with cisplatin).
Mentally unable to understand the nature, objectives, and possible consequences of the study or refusing its constraints.
A congenital or hereditary disease known to decrease hearing function (e.g. Otoferlin [OTOF]-related deafness).
Any medical history affecting the middle ear function such as chronic otitis, cholesteatoma, or tympanic membrane perforation.
Any inner ear disease that is likely to decrease hearing function according to the Investigator’s judgment (e.g. herpes zoster oticus; Meniere’s disease; purulent labyrinthitis; vestibular schwannoma).
Having a history of sudden sensory neural hearing loss.
Having a fluctuating hearing loss (e.g. due to Meniere’s disease, vestibular aqueduct syndrome, or autoimmune inner ear disease).
History of head trauma with hearing loss.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Study Arm B (treatment arm) SENS-401 (R-Azasetron Besylate) Subjects receiving 43.5 mg of oral SENS-401 b.i.d for up to 23 weeks. This arm will provide data on the potential protective effects of SENS-401 on cisplatin induced ototoxicity.
- Primary Outcome Measures
Name Time Method Change from baseline of the average of the hearing threshold of 3 contiguous hearing frequencies assessed with a 0.5-12.5 kHz audiogram 4 weeks after the completion of the last cisplatin treatment in each eligible ear of each subject. Change from baseline of the average of the hearing threshold of 3 contiguous hearing frequencies assessed with a 0.5-12.5 kHz audiogram 4 weeks after the completion of the last cisplatin treatment in each eligible ear of each subject.
- Secondary Outcome Measures
Name Time Method Please cf Protocol (there is too many caracters to be put here) Please cf Protocol (there is too many caracters to be put here)
Trial Locations
- Locations (11)
CHU Henri Mondor
🇫🇷Creteil, France
Centre Medico Chirurgical Ambroise Pare Hartmann
🇫🇷Neuilly-Sur-Seine, France
Hopital Europeen Georges Pompidou
🇫🇷Paris, France
Hopitaux Universitaires Pitie Salpetriere
🇫🇷Paris, France
Centre Oscar Lambret
🇫🇷Lille, France
Centre Hospitalier Groupe Hospitalier De La Rochelle Re Aunis
🇫🇷La Rochelle, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Centre Hospitalier Universitaire De Saint Etienne
🇫🇷St Etienne Cedex 2, France
Hospital Edouard Herriot
🇫🇷Lyon Cedex 03, France
Hopital Saint Louis
🇫🇷Paris, France
Scroll for more (1 remaining)CHU Henri Mondor🇫🇷Creteil, FranceChristophe TOURNIGANDSite contact0556333333christophe.tournigand@hmn.aphp.fr