Add Pedmark to cisplatin chemotherapy to prevent hearing loss in men with stage II–III metastatic testicular germ cell tumors

Phase 1 Trial of Pedmark in Men Receiving Cisplatin for Metastatic Germ Cell Tumor

We will test whether adding Pedmark to cisplatin chemotherapy reduces hearing damage in men with stage II–III metastatic testicular germ cell tumors.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: City of Hope Medical Center (other)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 1 site (Duarte, California)
• Trial ID: NCT07218913 on ClinicalTrials.gov

What this trial studies

This phase I randomized trial compares standard cisplatin-based chemotherapy with or without sodium thiosulfate (Pedmark) in adult men with stage II–III metastatic testicular germ cell tumors. Participants receive 3–4 cycles of standard cisplatin-containing regimens given on 21-day cycles, with the experimental arm also receiving Pedmark, and undergo serial audiometry and imaging (CT/MRI). The study measures incidence of clinically meaningful ototoxicity as the primary outcome and examines high-frequency hearing loss, severity/progression of ototoxicity, safety/tolerability, tinnitus, and disease response at six months as secondary and exploratory outcomes. Safety monitoring and audiometric testing are performed throughout treatment to track hearing changes and adverse events.

Who should consider this trial

Good fit: Men aged 18 or older with histologically confirmed stage II–III metastatic testicular germ cell tumors who are planned for first- or second-line cisplatin-based chemotherapy with a cumulative cisplatin dose ≥300 mg/m^2, have ECOG 0–1 (or Karnofsky ≥70), measurable disease, and can complete baseline and serial audiometry are ideal candidates.

Not a fit: Patients not receiving cisplatin, those with planned cumulative cisplatin exposure below 300 mg/m^2, individuals with severe pre-existing hearing loss that prevents reliable baseline audiometry, or those unable to travel to the study site are unlikely to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, Pedmark could substantially reduce the risk of cisplatin-induced hearing loss and help preserve long-term hearing and quality of life for these patients.

How similar studies have performed: Sodium thiosulfate (Pedmark) has demonstrated reduced cisplatin ototoxicity and is FDA-approved for pediatric use, but randomized adult data are limited and adult efficacy remains less well established.

Eligibility criteria

Inclusion Criteria:

* 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
* Hemoglobin ≥ 9g/dL

  * NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment unless cytopenia is secondary to disease involvement
* Total bilirubin ≤ 1.5 X upper limit of normal (ULN)

  * Patients with known Gilbert disease who have serum bilirubin level \< 3 x ULN may be enrolled
* Aspartate aminotransferase (AST) ≤ 3.0 x ULN
* Alanine aminotransferase (ALT) ≤ 3.0 x ULN
* Creatinine clearance of ≥ 60 mL/min per the Cockcroft-Gault formula or serum creatinine ≤ 1.5 x ULN
* \* If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN

  * If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
* \* If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN

  * If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
* Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 11 months after the last dose of cisplatin for injection

Exclusion Criteria:

* 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)

Where this trial is running

Duarte, California

• City of Hope Medical Center — Duarte, California, United States (RECRUITING)

Study contacts

• Principal investigator: Alex Chehrazi-Raffle — City of Hope Medical Center

Conditions: Hearing Loss, Metastatic Malignant Germ Cell Tumor, Metastatic Malignant Nongerminomatous 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