Phase 1 Trial of Pedmark in Men Receiving Cisplatin for Metastatic Germ Cell Tumor
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Incidence of clinically meaningful ototoxicity
研究概览
简要总结
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.
详细描述
PRIMARY OBJECTIVE:
I. Evaluate the incidence of clinically meaningful ototoxicity in adults with metastatic germ cell tumor (GCT) receiving sodium thiosulfate anhydrous (Pedmark) plus cisplatin-based chemotherapy compared to those receiving cisplatin-based chemotherapy alone.
SECONDARY OBJECTIVES:
I. Assess the incidence of high-frequency ototoxicity (affecting frequencies within 8000-12,500 Hz) between adults in both arms.
II. Assess the severity and progression of ototoxicity between adults in both arms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Arm I (SOC cisplatin)
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.
干预措施: Audiometric Test (Procedure)
Arm I (SOC cisplatin)
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.
干预措施: Cisplatin (Drug)
Arm II (SOC cisplatin, Pedmark)
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.
干预措施: Computed Tomography (Procedure)
Arm II (SOC cisplatin, Pedmark)
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.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm II (SOC cisplatin, Pedmark)
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.
干预措施: Sodium Thiosulfate Anhydrous (Drug)
Arm I (SOC cisplatin)
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.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm I (SOC cisplatin)
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.
干预措施: Computed Tomography (Procedure)
Arm II (SOC cisplatin, Pedmark)
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.
干预措施: Audiometric Test (Procedure)
Arm II (SOC cisplatin, Pedmark)
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.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Incidence of clinically meaningful ototoxicity
时间窗: Up to 6 months post-treatment
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.
次要结局
- 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)