Intravenous Magnesium in Patients Receiving Cisplatin

Study Overview
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Brief Summary
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This research study, is trying to determine the highest dose of magnesium that can be given safely to people with malignant mesothelioma receiving intraoperative chemotherapy with cisplatin who are at risk for acute kidney injury. The name(s) of the study drug involved in this study is magnesium sulfate.

Detailed Description
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This research study is a phase 1 pilot study, which is the first time investigators are examining larger doses of magnesium in patients receiving cisplatin and the effect of intravenous magnesium administration on blood magnesium levels. In previous studies it was found that patients with lower blood magnesium levels were at higher risk of acute kidney injury. The study is looking to determine the best dose(s) of intravenous magnesium to administer safely without severe or unmanageable side effects in participants. The purpose of the study is also to determine the dose of intravenous magnesium needed to achieve a target level. The U.S. Food and Drug Administration (FDA) has not approved magnesium for people with mesothelioma receiving cisplatin but it has been approved for other uses. The research study procedures include: screening for eligibility and study treatment at participant's preoperative visit with their thoracic surgeon. Intravenous magnesium will be administered in the hospital, the night prior to surgery, and take place over 36 hours. Participants will followed for 4 days on postoperative days 1, 2, and 3. It is expected that about 10 people will take part in this research study.

Official Title
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Pilot and Feasibility Study of Intravenous Magnesium in Patients Receiving Hyperthermic Intraoperative Chemotherapy With Cisplatin (HIOCC)

Conditions
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Mesothelioma

Intervention / Treatment
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* Drug: Magnesium Sulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥18 years with malignant mesothelioma admitted for HIOCC. Because no dosing or adverse event data are currently available on the use of intravenous magnesium participants <18 years of age, children are excluded from this study, but will be eligible for future pediatric studies. Glomerular filtration rate (GFR)≥ 30 ml/min/1.73m2 at the time of enrollment Patients must have the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Patients with a pre-treatment serum Magnesium level >2.5 mg/dl or <1.3 mg/dl at the preoperative visit Patients with AKI at the time of enrollment, assessed by Kidney Disease Improving Outcomes Criteria (serum creatinine increase ≥1.5x baseline) Patients with estimated glomerular filtration rate <30 ml/min/1.73m2 at the time of enrollment Patients with neuromuscular disease (e.g., amyotrophic lateral sclerosis, multiple sclerosis, muscular dystrophy, myasthenia gravis, myositis) Patients with sustained bradycardia (heart rate <50 beats per minute on 1 or more EKGs in the preceding 90 days) or 2nd degree AV heart block type 2 or higher with the absence of a functioning pacemaker Participants who are receiving any other investigational agents. History of allergic reactions attributed to compounds of similar chemical or biologic composition to intravenous magnesium Participants with uncontrolled intercurrent illness. Participants with psychiatric illness/social situations that would limit compliance with study requirements. Pregnant women are excluded from this study because they may need magnesium for treatment of preeclampsia or eclampsia, apart from this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Magnesium Sulfate<br>Starting the night before surgery participants will receive intravenous infusion of magnesium over approximately 36 hours. Dosage amounts will vary among participants as the study is determining the highest dose of magnesium that can be administered safely without severe or unmanageable side effects. The first 5 participants of the study will all receive the same dose of magnesium. The decision to test other doses of magnesium in 5 additional participants will depend on magnesium levels and dose tolerance outcomes in the first 5 participants. Participants will be followed for 4 days and undergo blood test to measure magnesium levels at the time of hospital admittance, the morning prior to the surgery, twice immediately after surgery, and twice a day for 3 days after the surgery. | Drug: Magnesium Sulfate<br>* Intravenous infusion of magnesium sulfate prior to intraoperative chemotherapy with cisplatin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility and acceptability as measured by participant rates of enrollment | Feasibility assessed by % of patients that agree to participate. Project feasible if >30% of the patients approached agree to participate | 6 months | 
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0 | NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | Time of magnesium infusion till 2 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Magnesium Level | Assess the amount of IV magnesium needed to reach a target level of 3 to 4.8mg/dl. Magnesium levels will be measured at multiple time points. We want >80% (≥32/40) of the time-averaged, postoperative magnesium levels to be within the target range of 3 to 4.8 mg/dl. | Day of surgery through postoperative day 3. | 
| Tubular Injury Markers | Changes in urinary KIM-1 and urinary NGAL levels in order to assess intra- and interassay variability | From admission through postoperative day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesothelioma, Magnesium Sulfate, intraoperative cisplatin