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