Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors

NCT07218913 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 25407NCI-2025-07298P30CA033572
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial evaluates whether adding Pedmark to standard of care cisplatin-based chemotherapy reduces drug-induced ear damage (ototoxicity) in men with stage II-III testicular germ cell tumors that have spread from where they first started (primary site) to other places in the body (metastatic). Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Cisplatin-induced ototoxicity remains a major concern in adult patients with germ cell tumors as nearly four out of five patients develop hearing loss after treatment. Cisplatin is thought to cause ear damage by the production of chemically reactive molecules called reactive oxygen species. These molecules can cause damage when their levels get too high. Pedmark may reduce the negative side effects of cisplatin by neutralizing these reactive molecules. Pedmark has been approved for reducing the risk of cisplatin-induced ototoxicity in pediatric patients and older patients with solid tumors that haven't spread to other parts of the body. Adding Pedmark to cisplatin-based chemotherapy treatment may reduce ototoxicity in adult men with stage I-III testicular metastatic germ cell tumors.

Conditions

Metastatic Malignant Nongerminomatous Germ Cell Tumor; Hearing Loss; Metastatic Malignant Germ Cell Tumor; Metastatic Malignant Testicular Non-Seminomatous Germ Cell Tumor; Metastatic Testicular Seminoma; Stage II Testicular Cancer AJCC v8; Stage III Testicular Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Incidence of clinically meaningful ototoxicity

  Will compare the proportion of patients who experience clinically meaningful ototoxicity between adults with germ cell tumor (GCT) receiving Pedmark plus cisplatin-based chemotherapy compared to those receiving cisplatin-based chemotherapy alone. Clinically meaningful ototoxicity is defined by a \> 20 decibel (dB) threshold shift at a single frequency, a \> 10 dB shift at two adjacent frequencies, or a change to "no response" at three consecutive frequencies as long as these frequencies fall between 250-8000 hertz (Hz) which impacts speech understanding. The corresponding 95% confidence interval (CI) will be constructed using the Clopper-Pearson exact method. The proportion of patients who develop clinically meaningful ototoxicity will be compared between arms using a one-sided Fisher's exact test.

  Up to 6 months post-treatment

Secondary Outcomes (4)

• Incidence of high-frequency ototoxicity

  Up to 6 months post-treatment

• Degree of ototoxicity

  Baseline to 1, 3, and 6 months post-treatment

• Incidence of adverse events (AEs)

  Up to 6 months post-treatment

• Progression-free survival (PFS)

  From start of treatment to time of progressive disease or death, assessed up to 2 years

Study Arms (2)

Arm I (SOC cisplatin)

ACTIVE COMPARATOR

Patients receive cisplatin IV over 60 minutes on days 1-5 or 2-5 of each SOC cisplatin-based chemotherapy regimen cycle. Cycles repeat every 21 days for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial.

Procedure: Audiometric Test; Drug: Cisplatin; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Arm II (SOC cisplatin, Pedmark)

EXPERIMENTAL

Patients receive cisplatin IV over 60 minutes on days 1-5 or 2-5 of each SOC cisplatin-based chemotherapy regimen cycle. Patients also receive Pedmark IV over 30 minutes, 6 hours after each SOC cisplatin infusion, on days 1-5 or 2-5 of each cycle. Cycles repeat every 21 days for 3-4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the trial.

Procedure: Audiometric Test; Drug: Cisplatin; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Sodium Thiosulfate Anhydrous

Interventions

Audiometric Test PROCEDURE

Ancillary studies

Also known as: Audiometric Testing, Audiometry, Hearing Test

Arm I (SOC cisplatin); Arm II (SOC cisplatin, Pedmark)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm I (SOC cisplatin); Arm II (SOC cisplatin, Pedmark)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm I (SOC cisplatin); Arm II (SOC cisplatin, Pedmark)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm I (SOC cisplatin); Arm II (SOC cisplatin, Pedmark)

Sodium Thiosulfate Anhydrous DRUG

Given IV

Also known as: Disodium Thiosulfate, Sodium Thiosulfate, Anhydrous, Thiosulfuric Acid, Disodium Salt

Arm II (SOC cisplatin, Pedmark)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Willing and able to sign informed consent form
• Willing and able to participate in baseline and serial audiometry exams
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) of 0 or 1 or Karnofsky score ≥ 70
• Histologically confirmed germ cell tumor (seminoma or non-seminoma)
• Presence of metastatic disease (stage II or III)
• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
• Receiving first or second line cisplatin-based chemotherapy
• Planned cumulative cisplatin dose of ≥ 300mg/m\^2 (including previous treatment)
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
• Platelets ≥ 100,000/mm\^3
• NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement

You may not qualify if:

• Any cisplatin-based therapies within 4 weeks prior to initiation of study treatment
• If cisplatin infusion during study is planned to be longer than 6 hours, as Pedmark safety and efficacy has not been established when administered following longer cisplatin infusions
• Chronic steroid use, defined as greater than prednisone 5 mg daily for longer than 21 days (steroids used as antiemetic during treatment is permitted)
• Concurrent use of other ototoxic drugs other than cisplatin (loop diuretics, aminoglycosides, etc)
• Patient must adhere to low sodium diet given other comorbidities
• History of severe hypersensitivity to sodium thiosulfate or any components such as sulfites or thiols
• Known symptomatic brain metastases, leptomeningeal carcinomatosis, or prior cranial irradiation
• Deemed cisplatin ineligible due to poor performance status, cardiac dysfunction, renal insufficiency, or significant peripheral neuropathy
• Greater than or equal to moderate hearing loss (HL) at baseline per World Health Organization (WHO) classification
• Unstable cardiac disease as defined by one of the following:
• Cardiac events such as myocardial infarction (MI) within the past 6 months
• NYHA (New York Heart Association) heart failure class III-IV
• Uncontrolled atrial fibrillation or hypertension
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Hearing Loss; Seminoma; Testicular Neoplasms

Interventions

Hearing; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Magnetic Resonance Spectroscopy; sodium thiosulfate

Condition Hierarchy (Ancestors)

Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Germinoma; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Vestibulocochlear Physiological Phenomena; Physiological Phenomena; Sensation; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Alex Chehrazi-Raffle

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2025
• First Posted: October 21, 2025
• Study Start: February 19, 2026
• Primary Completion (Estimated): January 22, 2031
• Study Completion (Estimated): January 22, 2031
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (1)