Magnesium supplementation therapy to prevent cisplatin-induced acute nephrotoxicity in pediatric cancer: Protocol for a randomised phase 2 trial.

JRCT ID: jRCTs031180251

Registered date:13/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Newly diagnosed malignant disease
• Date of first enrollment: 01/04/2019
• Target sample size: 80
• Study type: Interventional
• Intervention(s): In this study, participants will be randomised in equal populations into two arms. One arm will receive cisplatin-containing chemotherapy without Mg in the first course, then start Mg supplementation in the second course and subsequent even numbered course (arm AB). Another arm will receive cisplatin-containing chemotherapy with Mg supplementation from the first course, and then, Mg will be administered only in odd-numbered course (arm BA). In the group B chemotherapy course, Mg sulfate must be administered intravenously concomitant with sufficient volume of intravenous fluid (allowance 2,400-3,000 ml/m2/day).Dosage of the Mg supplementation is 15mEq/m2/day (allowance 13.5-16.5) starting from at least 12 hours prior to initiation of cisplatin infusion and continue until at least 24 hours after termination of cisplatin infusion. In the group A, Mg administration is allowed for patients who present hypomagnesemia less than 1.5 mg/dl and it must be done during the time without cisplatin administration.

Outcome(s)

• Primary Outcome: Primary endpoint is proportion of chemotherapy courses which result in elevated serum creatinine equal to, or more than 50% of the pre-value. Four secondary endpoints are (1) proportion of chemotherapy courses result in renal dysfunction by means of cystatin-C in serum, B2M, L-FABP, NGAL, and NAG in urine
• Secondary Outcome: Four secondary endpoints are (1) proportion of chemotherapy courses result in renal dysfunction by means of cystatin-C in serum, B2M, L-FABP, NGAL, and NAG in urine, (2) comparison between two groups of kinetics of cystatin-C in serum, B2M, L-FABP, NGAL, and NAG in urine during chemotherapy course, (3) comparison between two groups of kinetics of serum Mg value as a surrogate of pharmacokinetics of Mg sulfate, and (4) Safety analyses of Mg supplementation.

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: < 20age old
• Gender: Both

Include criteria

1. Newly diagnosed malignant disease.
2. Age less than 20 years.
3. Plan to undergo chemotherapy containing cisplatin equal or more than 60 mg/m2/course. Cisplatin must be administered in 1-day schedule, or 5-day schedule. Cycle of the chemotherapy courses must be equal to, or longer than 21 days for appropriate observation.
4. Eastern Clinical Oncology Group Performance Status 0, 1, or 2.
5. Written informed consent from participant (older than 16 years only) and guardian.

Exclude criteria

1. History of allergic reaction to magnesium.
2. Cardiac dysfunction necessitate medication.
3. Uncontrollable active infection.
4. Current use of hemodialysis.
5. Pregnancy or lactation.
6. Other problems which investigators judge inappropriate for study entry.

Related Information

• Primary Sponsor: Matsui Motohiro
• Source(s) of Monetary Support: The grant for general research in metropolitan hospitals from the Tokyo Metropolitan Government.,The Grant for Treatment Research in Children's Cancer Association of Japan