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Purpose

Single-center, open-label, two-stage pilot study examining the efficacy and safety of sparsentan for reducing high-grade proteinuria among patients with cancer who receive vascular endothelial growth factor inhibitors

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Adults (≥ 18 years old) with active malignancy who are currently treated with VSPIs 2. New high-grade proteinuria, defined as ≥ 2+ proteinuria on dipstick or a calculated urinary protein-to-creatinine ratio ≥ 1.0 g/g 3. Able to provide written inform consent

Exclusion Criteria

  1. Estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73m2 2. Baseline high grade proteinuria ≥ 2+ proteinuria on dipstick or a calculated urinary protein-to creatinine ratio or microalbumin-to-creatinine ≥ 1.0 g/g prior to VSPI initiation 3. Acute kidney injury defined as serum creatinine at least 1.5 times above the most proximal serum creatinine prior to VSPIs initiation 4. History of allergic reactions or angioedema to any angiotensin receptor blocker (ARB) or ERA, including sparsentan or irbesartan, or has a hypersensitivity to any of the excipients in the study medications. 5. Any potassium value >5 mEq/L in the 14 days preceding high-grade proteinuria 6. History of organ transplantation, with the exception of corneal transplants. 7. History of congestive heart failure (New York Heart Association Class II-IV) 8. History of clinically significant cerebrovascular disease (transient ischemic attack or stroke) and/or coronary artery disease (hospitalization for myocardial infarction or unstable angina, new onset of angina with positive functional tests, coronary angiogram revealing stenosis, or a coronary revascularization procedure) within 6 months prior to screening. 9. Jaundice, hepatitis, or known hepatobiliary disease (excluding asymptomatic cholelithiasis), or alanine aminotransferase and/or aspartate aminotransferase >2 times the upper limit of the normal at screening. 10. Body weight <50 kg at screening 11. Unable to hold renin-angiotensin-aldosterone system (RAAS) inhibitors such as angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), spironolactone, eplerenone, aliskiren, aldosterone blockers during run-in period 12. Concomitant use of the following medications: 1. Inhibitors of endothelin system such as ambrisentan, bosentan, macitentan 2. Potassium-sparing diuretics such as amiloride, triamterene 3. Antiarrhythmic medications such as amiodarone, digoxin 4. Weight loss medications such as orlistat or amphetamine derivative agents 5. St. John's wort or other hypericum-derived products 6. Strong CYP3A inhibitors such as ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, ritonavir- or cobicistat-boosted regimens, boceprevir, telaprevir, conivaptan, mibefradil 13. Pregnant or breastfeeding 14. Concurrent participation in a study with an alternative experimental therapy that may interact with sparsentan 15. Any condition that, in the view of the principal investigator, might place the patient at increased risk or compromise the integrity of the study 16. Conflict with other study

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Treatment with sparsentan, an endothelin-1 antagonist 		Participants will receive sparsentan 200 mg daily for 2 weeks, and will then titrate up to a target of 400 mg daily. After the Week 8 visit, patients will return to standard-of-care. We will compare the mean percent change in urine protein to creatinine ratio in patients treated with sparsentan versus historical controls who did not receive sparsentan.
  • Drug: sparsentan
    Participants will receive sparsentan 200 mg daily for 2 weeks, and will then titrate up to a target of 400 mg daily. Safety and feasibility will be assessed. The mean percent change in urine protein to creatinine ratio will be assessed from screening to week 8, and compared to historical controls not treated with sparsentan.
Placebo Comparator
Historical controls with high-grade proteinuria not treated with sparsentan 		Participants must meet all eligibility criteria, but did not receive sparsentan. Historical controls will be matched based on age, sex, race, stage and cancer type
  • Drug: No sparsentan
    Historical controls who did not receive sparsentan, and are matched to patients who are treated with sparsentan

Recruiting Locations

Brigham and Women's Hospital
Boston, Massachusetts 02115
Contact:
Shruti Gupta
571-236-6626
sgupta21@bwh.harvard.edu

More Details

Status
Recruiting
Sponsor
Brigham and Women's Hospital

Study Contact

Shruti Gupta, MD, MPH
5712366626
sgupta21@bwh.harvard.edu

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.