Efficacy and safety of intravenous magnesium for the prevention of cisplatin-induced nephrotoxicity in patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy: A phase II study. (MAGICIAN study (KDOG 2101))

JRCT ID: jRCTs031210300

Registered date:08/09/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: esophageal squamous cell carcinoma
• Date of first enrollment: 28/01/2022
• Target sample size: 30
• Study type: Interventional
• Intervention(s): Magnesium sulfate (8 mEq) will be administered before the administration of cisplatin as a IV infuison.

Outcome(s)

• Primary Outcome: Incidence of Grade > 2 serum creatinine elevation according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Secondary Outcome

1. Incidence and severity of nephrotoxicity based on creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR)
2. Changes in serum creatinine levels, Ccr and eGFR during neoadjuvant chemotherapy
3. Changes in urinary biomakers (N-acetyl-B-D-glucosaminidase (NAG), B2-microglobulin, and Liver-type fatty acid-binding protein (L-FABP)) during neoadjuvant chemotherapy
4. Change in serum magnesium level during neoadjuvant chemotherapy
5. Rates of chemotherapy dose delays, reductions, or discontinuations
6. Rates of changing chemotherapy regimen
7. Relative dose intensity
8. Evaluation of clinical and pathological responses according to the Response Evaluation Criteria in Solid Tumors (RECIST) and pathological criteria
9. Adverse event incidence based on CTCAE version 5.0
10. Incidence and severity of nephrotoxicity based on serum creatinine levels, Ccr, and eGFR for high-risk patients who have several risk factors for cisplatin-induced nephrotoxicity

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 80age old
• Gender: Both

Include criteria

1. A newly-diagnosed, histologically-confirmed esophageal squamous cell carcinoma
2. A resectable esophageal cancer with clinical stage I to III (UICC 8th edition)
3. Neoadjuvant chemotherapy regimen including high-dose cisplatin (> 70 mg/m2)
4. Age of 20 to 80 years old
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2
6. Adequate organ function:
- Absolute neutrophil count > 2,000/mm3
- Platelet count > 100,000/mm3
- Hemoglobin > 10.0 g/dL
- Total bilirubin < 1.5 mg/dL
- AST < 100 U/L, ALT < 100 U/L
- Creatinine clearance > 50 mL/min
7. Serum magnesium level < 3.0 mg/dL
8. Written informed consent

Exclude criteria

1. A history of chemotherapy for cancer in another organ
2. Use of a reduced dose of cisplatin from the time of initial treatment
3. A history of hypersensitivity to magnesium products
4. Having myasthenia gravis
5. A history of therapy for heart block
6. Pregnant or breast feeding women, women of child-bearing potential
7. Patients who are judged inappropriate for entry into this study by the investigator

Related Information

• Primary Sponsor: Watanabe Akinori
• Secondary Sponsor: Mohri Junichi
• Source(s) of Monetary Support: The Japan Society for the Promotion of Science