Clinical trial NCT04481672: Intravenous Magnesium in Patients Receiving Cisplatin
Official title: Pilot and Feasibility Study of Intravenous Magnesium in Patients Receiving Hyperthermic Intraoperative Chemotherapy With Cisplatin (HIOCC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Mesothelioma
Keywords: Mesothelioma
Magnesium Sulfate
intraoperative cisplatin
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
First posted: 2020-07-22
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Feasibility and acceptability as measured by participant rates of enrollment
timeFrame: 6 months
measure: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0
timeFrame: Time of magnesium infusion till 2 days.
Secondary outcomes:
measure: Magnesium Level
timeFrame: Day of surgery through postoperative day 3.
measure: Tubular Injury Markers
timeFrame: From admission through postoperative day 3
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Shruti Gupta, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: David E. Leaf, MD, MMSc
role: PRINCIPAL_INVESTIGATOR
References: