A phase II study of Pedmark (sodium thiosulfate anhydrate) to reduce ototoxicity induced by cisplatin for common malignancies in childhood and AYA (adolescent and young adult) patients

JRCT ID: jRCT2061220018

Registered date:19/05/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Ototoxicity induced by cisplatin for common malignancies
• Date of first enrollment: 09/09/2022
• Target sample size: 46
• Study type: Interventional

Intervention(s)

At 6 hours after cisplatin administration, the following amounts of sodium thiosulfate (PEDMARK) is administered by intravenous drip infusion for 15 minutes:
- Body weight over 10kg: 12.8 g/m^2
- Body weight 5-10kg: 75% 9.6 g/m^2
- Body weight under 5kg: 50% 6.4 g/m^2

Outcome(s)

• Primary Outcome: Ratio of hearing impairment using the ASHA (American Speech-Language-Hearing Association) assessment method at the end of the protcol treatment

Secondary Outcome

1. Evaluation of the safety of sodium thiosulfate
2. Antitumor efficacy.
3. Pharmacokinetic evaluation of sodium thiosulfate
4. Ratio of hearing impairment according to hearing assessment methods in Brock classification.

Key inclusion & exclusion criteria

• Age minimum: >= 1month old
• Age maximum: <= 30age old
• Gender: Both

Include criteria

1.Untreated patients with histologically or clinically diagnosed localized stage solid tumors. (neuroblastoma, hepatoblastoma, germinoma, osteosarcoma, soft tissue sarcoma, medulloblastoma, atypical teratoid rhabdoid tumor, etc.)
2.Patients are scheduled to receive anti-cancer therapy that includes total cumulative dose 200 mg/m^2 and over cisplatin (each dose to be completed within 6 hours).
3.Written consent has been obtained from adult patients or the legally acceptable representative of minor patients for participation in the study. For minor patients, explanations should be provided and written consent should be obtained using an assent document as much as possible.
4.Age at informed consent is between 3 and 18 years for the primary cohort, and between 1 month and 3 years or between 19 and 30 years for the exploratory cohort.
5.The following criteria for audiometric testing must be met
- Patients aged 3 years or older must have a pure tone audiogram (air conduction) with all ratings of 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz and 8000 Hz at 20 dB or less. The type of pure tone audiometry shall be a standard pure tone audiometry in principle. But a pure tone play audiometry (air conduction) shall be acceptable if a standard pure tone audiometry is not available for ages 3 to 6. In addition, only patients for ages of 3 to 6 who do not meet the criteria above can be enrolled if the value is 20 dB or less after performing the following tests in the order of 1) to 3).
1) Auditory brainstem reflex (ABR) tone burst (air conduction) 500Hz, 1000Hz, 2000Hz, 4000Hz, 8000Hz
2) ABR tone burst (air conduction) 500Hz, 1000Hz, 2000Hz, 4000Hz
3) ASSR (air conduction) 500Hz, 1000Hz, 2000Hz, 4000Hz
- Patients aged 2 years or youger must be satisfied with either of the following criteria and be judged by the investigator to have no obvious hearing impairment.
+ Conditioned Orientation Response audiometry (COR) at 25dB or less in one of the measured ranges.
+ Visual Reinforcement Audiometry (VRA) at 25 dB or less in one of the measured ranges.
+ ASSR (air conduction) at 20 dB or less in one of the measured ranges.
6.Good PS.
7.Meeting that the latest examination within 14 days before enrollment to the given criteria.
8.Normal cardiac function within 28 days before enrollment to the given criteria.
9.For women of childbearing potential, a negative pregnancy test within 14 days before enrollment has been confirmed. Women of childbearing potential or men having a woman partner of childbearing potential have agreed to use appropriate contraceptive methods for duration of the study.

Exclude criteria

1.Advanced stage disease or recurrent disease (the high risk group for neuroblastoma, childhood liver tumor, extracranial germ cell tumors or atypical teratoid rhabdoid tumor and medulloblastoma, osteosarcoma or intracranial germ cell tumor, etc., in the presence of metastatic).
2.History of chemotherapy including treatment for other cancer types.
3.History of hypersensitivity to sodium thiosulfate.
4.History of arrhythmia requiring treatment.
5.Cannot or may not be able to follow the protocol for any reason.
6.Cannot or may not be able to perform audiometry for any reason.
7.Difficulty participating in the study due to psychosis or psychiatric symptoms.
8.Pregnant, breastfeeding or possibly pregnant or willing to be pregnant.

Related Information

• Primary Sponsor: Hiyama Eiso
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development