Protecting the Kidney's Proximal Tubules From Platinum-Based Chemotherapy Toxicity

NCT07018622 | Recruiting Phase 2 DMC

• 1 other identifier: NMM-5274
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with cancer who receive platinum-based chemotherapy are at increased risk of kidney injury caused by these drugs. This form of toxicity can lead to treatment delays, dose reductions, or permanent discontinuation of chemotherapy, all of which can negatively impact cancer outcomes and increase patient morbidity. Despite the clinical significance, there are currently no effective strategies to prevent platinum-induced kidney damage. Existing preventive measures-such as hydration, mannitol use, and magnesium supplementation-are limited and not always effective. This clinical trial investigates whether a type of medication known as a Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor, specifically dapagliflozin, can protect the kidneys from damage during platinum-based chemotherapy in patients with solid tumors. Researchers believe that blocking SGLT2 in the kidney may reduce toxicity in the proximal tubules-the area most affected by platinum drugs. The primary goal of this study is to compare the levels of a specific urinary biomarker of kidney injury (called KIM-1) 72 hours after chemotherapy, between patients who receive dapagliflozin and those who receive a placebo. Lower levels of this biomarker may indicate that dapagliflozin is helping protect the kidneys. Secondary goals include comparing additional urinary biomarkers of kidney damage and function-such as EGF (epidermal growth factor), N-acetyl-β-D-glucosaminidase (uNAG), albumin (AlbU), and β2-microglobulin (uβ2-m)-at 72 hours and 7 days after chemotherapy. The study will also assess: The percentage of patients who develop acute kidney injury, Changes in estimated glomerular filtration rate (a measure of kidney function), Electrolyte abnormalities (sodium, magnesium, phosphorus), And any adverse events associated with dapagliflozin use. As exploratory objectives, the trial will also evaluate cancer treatment response between groups (using RECIST 1.1 criteria) and the overall safety and tolerability of dapagliflozin compared to placebo. This is a randomized, double-blind, placebo-controlled clinical trial, meaning that participants will be randomly assigned to receive either dapagliflozin or a placebo, and neither the patients nor the study team will know who receives which treatment until the study ends. The central hypothesis is that dapagliflozin will reduce urinary biomarkers of kidney injury by at least 50% compared to placebo, offering a potential protective strategy against platinum-induced nephrotoxicity without interfering with cancer treatment.

Conditions

Solid Tumors; Cisplatin Nephrotoxicity

Keywords

Solid Tumors; Platinum-Based Chemotherapy; Cisplatin; Carboplatin; Nephrotoxicity; Kidney Tubules, Proximal; SGLT2 Inhibitors; Kidney Injury Molecule-1; Renal Protection; Chemotherapy-Induced Kidney Injury; Randomized Controlled Trial; Urinary Biomarkers; Dapagliflozin

Outcome Measures

Primary Outcomes (1)

• Urinary KIM-1/Creatinine (uKIM-1/Cr) expression at 72 hours

  Measurement of urinary KIM-1 normalized to creatinine (uKIM-1/Cr \[pg/mg\]) to evaluate renal tubular injury at 72 hours after platinum-based chemotherapy, comparing dapagliflozin vs. placebo.

  72 hours (Day 3) after platinum administration

Secondary Outcomes (8)

• Urinary Epidermal Growth Factor levels adjusted by creatinine (EGF/Cr)

  Baseline to Day 3 and Day 7

• Urinary N-acetyl-β-D-glucosaminidase levels adjusted by creatinine (uNAG/Cr)

  Baseline to Day 3 and Day 7

• Urinary Albumin levels adjusted by creatinine (AlbU/Cr)

  Baseline to Day 3 and Day 7

• Urinary β2-microglobulin levels adjusted by creatinine (uβ2-m/Cr)

  Baseline to Day 3 and Day 7

• Urinary Kidney Injury Molecule-1 levels adjusted by creatinine (KIM-1/Cr)

  Baseline to day 7 after platinum administration

Other Outcomes (2)

• Electrolyte abnormalities (sodium, magnesium, phosphorus) at 72 hours and Day 7

  72 hours (Day 3), 168 hours (Day 7) after platinum administration

• Oncologic response by RECIST 1.1 criteria

  Up to 24 weeks post-randomization

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

This arm aims to evaluate the potential nephroprotective effect of SGLT2 inhibition using urinary biomarkers of tubular injury.

Drug: Dapagliflozin 10 MG Oral Tablet

Placebo

PLACEBO COMPARATOR

This group serves as a control to evaluate the efficacy and safety of dapagliflozin in preventing platinum-induced nephrotoxicity.

Drug: Placebo Oral Tablet

Interventions

Placebo Oral Tablet DRUG

Participants in this arm will receive a matched oral placebo starting one day before platinum-based chemotherapy infusion (cisplatin or carboplatin) and continuing for 72 hours. Standard supportive care including hydration and magnesium supplementation will also be provided. Investigators and participants will remain blinded to the group assignments.

Also known as: Matching placebo

Placebo

Dapagliflozin 10 MG Oral Tablet DRUG

Participants in this arm will receive oral dapagliflozin 10 mg daily starting one day before platinum-based chemotherapy infusion (cisplatin or carboplatin) and continuing for 72 hours. The intervention aims to assess the potential nephroprotective effect of SGLT2 inhibition. Standard supportive care including hydration and magnesium supplementation will be provided to all participants.

Also known as: Forxiga, AZD2281

Dapagliflozin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form
• Diagnosis of a solid tumor requiring a platinum-based chemotherapy regimen (cisplatin or carboplatin)
• Expected survival \> 4 months
• ECOG performance status 0-2

You may not qualify if:

• History of nephrectomy
• History of kidney transplant
• Concurrent use of known nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, cyclophosphamide, ifosfamide, methotrexate)
• Type 1 diabetes mellitus
• Poorly controlled type 2 diabetes (HbA1c \> 8% or fasting glucose \> 200 mg/dL in the past month)
• Active glomerulopathy
• Prior use of SGLT2 inhibitors or current indication for their use
• eGFR \< 20 ml/min/1.73 m²
• Active urinary tract infection
• Unresolved obstructive uropathy
• Participation in another clinical trial
• History of recurrent genitourinary infections

Sponsors & Collaborators

• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: lead

Study Sites (1)

Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán"

México, Tlalpan, 14080, Mexico

RECRUITING

MeSH Terms

Interventions

dapagliflozin; olaparib

Study Officials

• Juan M Mejía-Vilet, PhD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erick Y Zuñiga, MD

CONTACT

+ 52 55 5487 0900; erick.zunigag@incmnsz.mx

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2025
• First Posted: June 12, 2025
• Study Start: May 7, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): October 30, 2026
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

ME (1)