Ph. I/II Sodium Thiosulfate for OtoProtection During Cisplatin (STOP-CIS)

• Pedmark® STS (Drug): Pedmark® STS (20 g/m2) will be given via intravenous infusion over 15-30 minutes, starting 6 hours after the completion of cisplatin infusion. Pedmark® STS will be given each day of cisplatin infusion.

Primary outcomes

• Efficacy of intravenous STS to reduce hearing impairment associated with cisplatin [Baseline, after cumulative cisplatin dose (≥ 200 mg/m2), and at 3 months following the conclusion of cisplatin chemotherapy treatment.]: Proportion of participants with Brock grade ≥1 hearing loss determined from audiometry exams. The Brock ototoxicity classification and grading scale are as follows: Grade 0 = hearing threshold less than 40 dB HL at all test frequencies; Grade 1 = hearing threshold greater than or equal to 40 dB HL at 8 kHz only; Grade 2 = hearing threshold greater than or equal to 40 db HL at 4kHz and above; Grade 3 = hearing threshold greater than or equal to 40 dB HL at 2 kHz and above; Grade 4 = hearing threshold greater than or equal to 40 dB HL at 1 kHz and above.

Secondary outcomes

• Tolerability of the administration of STS based on the adverse events [At the end of treatment, up to 12 months from baseline.]: Overall safety profile characterized by the type, frequency, severity, duration, and relationship to STS of any adverse events.
• Tolerability of the administration of STS: emetic control. [At the end of treatment, up to 12 months from baseline.]: Emetic control (episodes nausea and/or vomiting) will be documented during the clinic visit or hospital stay as per standard practice and assessed using the MASCC Antiemesis Tool (MAT).
• Cisplatin pharmacokinetics: area under the plasma concentration versus time curve (AUC) [At the first study treatment visit]: A noncompartmental pharmacokinetic analysis of total and unbound cisplatin will be performed with Phoenix WinNonlin v8.5 (Certara), using a linear method to calculate the area under the plasma concentration versus time curve (AUC) at 4 and 6 hours post-cisplatin dose at the first study treatment visit.
• Cisplatin pharmacokinetics: peak plasma concentration (Cmax) [At the first study treatment visit]: A noncompartmental pharmacokinetic analysis of total and unbound cisplatin will be performed with Phoenix WinNonlin v8.5 (Certara), using a linear method to calculate the peak plasma concentration (Cmax) at 4 and 6 hours post-cisplatin dose at the first study treatment visit.
• Cisplatin pharmacokinetics: elimination rate constant [At the first study treatment visit]: A noncompartmental pharmacokinetic analysis of total and unbound cisplatin will be performed with Phoenix WinNonlin v8.5 (Certara), using a linear method to calculate the elimination rate constant at 4 and 6 hours post-cisplatin dose at the first study treatment visit.
• Cisplatin pharmacokinetics: half-life [At the first study treatment visit]: A noncompartmental pharmacokinetic analysis of total and unbound cisplatin will be performed with Phoenix WinNonlin v8.5 (Certara), using a linear method to calculate the half-life at 4 and 6 hours post-cisplatin dose at the first study treatment visit.
• Cisplatin pharmacokinetics: total body clearance [At the first study treatment visit]: A noncompartmental pharmacokinetic analysis of total and unbound cisplatin will be performed with Phoenix WinNonlin v8.5 (Certara), using a linear method to calculate the total body clearance at 4 and 6 hours post-cisplatin dose at the first study treatment visit.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Participants have provided informed consent prior to initiation of any study-specific activities.
* At least 18 years of age, male or female, at the time of signing the informed consent.
* ECOG Performance Status 0-1
* Histologically or cytologically confirmed treatment-naïve cancer.
* Scheduled to receive an FDA-approved, on-label indication, standard of care systemic cisplatin-based regimen (at least 200 mg/m2 cumulative dose) for any untreated any solid malignancy deemed by the treating physician

Exclusion Criteria:

* Prior cisplatin exposure due to a cancer treatment history
* Concurrent ototoxic medication unable to be safely discontinued or switched to a non-toxic alternative
* Planned radiation to the head or neck prior to, during, or within 3 months of completion of cisplatin
* History of severe hypersensitivity to sulfite, sodium thiosulfate, or any components
* Baseline serum sodium > 145 mmol/L or any grade ≥ 3 electrolyte abnormality
* Cisplatin infusion duration greater than 6 hours
* Females during pregnancy or breastfeeding, and childbearing potential, unwilling to use a method of contraception during treatment
* Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment
* Subject likely not to be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (i.e., Clinical Outcome Assessments) to the best of the subject's and investigator's knowledge.
* History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.

• Lisa Davis, PharmD, Study chair, University of Arizona
• Alejandro Recio-Boiles, MD, Principal investigator, University of Arizona