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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

ConditionsHearing LossMetastatic Malignant Germ Cell TumorMetastatic Malignant Nongerminomatous Germ Cell TumorMetastatic Malignant Testicular Non-Seminomatous Germ Cell TumorMetastatic Testicular SeminomaStage II Testicular Cancer AJCC v8Stage III Testicular Cancer AJCC v8
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexMale
Age18+
SponsorCity of Hope Medical Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Audiometric Test

    Procedure/Surgery

    Ancillary studies

  • Cisplatin

    Drug

    Given IV

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Sodium Thiosulfate Anhydrous

    Drug

    Given IV

Treatment groups

44 Participants
are divided into 2 treatment groups
Group A: Arm I (SOC cisplatin)Active comparator 4 interventions
Group B: Arm II (SOC cisplatin, Pedmark)Experimental treatment 5 interventions

Trial outcomes

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.

Time frame
Up to 6 months post-treatment

Secondary outcomes

1

Incidence of high-frequency ototoxicity

Will compare the proportion of patients who experience high-frequency ototoxicity between adults with GCT receiving Pedmark plus cisplatin-based chemotherapy compared to those receiving cisplatin-based chemotherapy alone. High frequency ototoxicity is defined by a \> 20 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 8000-12,00 Hz. Will be estimated with 95% CIs by the Clopper-Pearson exact method. The proportion of patients who develop high-frequency ototoxicity will be compared between arms using a one-sided Fisher's exact test.

Time frame
Up to 6 months post-treatment
2

Degree of ototoxicity

Audiometry results between adults with GCT receiving Pedmark plus cisplatin-based chemotherapy will be compared to those receiving cisplatin-based chemotherapy alone. This will be decided by the audiologist per World Health Organization classification. Longitudinal changes in degree of ototoxicity will be summarized descriptively and analyzed using repeated-measures models to compare changes from baseline across time points between treatment arms.

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

Incidence of adverse events (AEs)

Will evaluate the rate of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 in adults with GCT receiving Pedmark plus cisplatin-based chemotherapy compared to those receiving cisplatin-based chemotherapy alone. The safety evaluation will be based on all patients that received at least one dose of the drug and will include AEs, serious AEs, and changes from baseline in laboratory evaluations, vital signs, and physical examinations. Summaries will be provided overall and by treatment group. The number and percentage of subjects reporting will be summarized overall and by CTCAE grade. All patients will be evaluable for toxicity from the time of their first treatment with cisplatin-based chemotherapy ± Pedmark.

Time frame
Up to 6 months post-treatment
4

Progression-free survival (PFS)

Will be assessed per Response Evaluation Criteria in Solid Tumors version 1.1. The difference in PFS between treatment arms will be estimated using the Kaplan-Meier method, with survival curves generated for each group. Statistical comparison of PFS between arms will be conducted using the log-rank test.

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

City of Hope Medical Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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