Effect of PARP Inhibitors on Glomerular Filtration Rate

January 20, 2022 updated by: University of Pennsylvania
The purpose of this study is to observe whether PARP inhibitors have an effect on serum creatinine level, and whether this reflects a change in creatinine secretion or a true change in kidney function.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

PARPi medications interact with transporters along the renal tubules involved in the secretion of creatinine and an increase in serum creatinine is often observed in patients treated with these agents; however, it is not known whether PARP inhibitors are associated with an actual change in the glomerular filtration rate, or if the observed elevations of serum creatinine are a result of a drug effect on creatinine secretion unrelated to changes in kidney function. The investigators therefore propose a prospective observational study to examine the incidence of elevation in serum creatinine from baseline levels in patients initiated on PARP inhibitors and compare the estimated glomerular filtration rate based on creatinine to that from alternative tests.

The primary purposes of this study are to:

  • Assess the incidence of increase in serum creatinine in patients with a solid-organ cancer on treatment with a PARP inhibitor.
  • To compare the estimated glomerular filtration rate based on serum creatinine with that of alternative biomarkers to assess whether changes in serum creatinine reflect changes in kidney function or creatinine secretion.
  • To examine the persistence or resolution of creatinine increase and/or GFR decrease noted after discontinuation of PARPi

Study Type

Observational

Enrollment (Actual)

2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

All patients will be recruited from the medical and gynecologic oncology practices at the Abramson Cancer Center / University of Pennsylvania. Patients that are 18+ years or older with a solid organ cancer who are being initiated on PARP inhibitor therapy.

Description

Inclusion Criteria:

  • Adult patients age 18 years or older
  • Diagnosed with any solid organ cancer
  • Planned to receive a PARP inhibitor (olaparib, niraparib, rucaparib, veliparib, or talazoparib)
  • Able to consent to study related procedures
  • If unable to give informed consent, must have healthcare proxy or legally authorized representative
  • Fluent in conversational English (Informed Consent form currently in English language)

Exclusion Criteria:

  • Patients who will not receive ongoing cancer care at Penn Medicine
  • Major psychiatric illness or cognitive impairment that in the judgment of the study investigators or study staff would preclude study participation
  • Any patients who are unable to comply with the study procedures as determined by the study investigators or study staff
  • Patients on dialysis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Individuals with solid tumors receiving PARPi

Kidney function will be assessed by serum creatinine, serum cystatin C, and urine creatinine clearance calculation for patients who opt-in to 24 hour urine collection.

These laboratory measures will be completed by patients at the following time points:

  • Timepoint A: Baseline (prior to PARP inhibitor initiation, at the time of standard of care clinical testing)
  • Timepoint B: On-treatment (within 3-9 weeks of PARP inhibitor initiation, at the time of standard of care clinical testing)
  • Timepoint C: Post-treatment (within 4 weeks of PARP inhibitor discontinuation, only for those patients with clinically significant changes in GFR based on serum creatinine, cystatin C, or 24 hour urinalysis at Timepoint B
Other: Kidney Function Test
Cystatin-C measurement

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in eGFR from Baseline to On-Treatment, 3-9 weeks after PARPi Initiation (Time Point B)
Time Frame: Study labs will be obtained within 3-9 weeks after PARPi is initiated
Change in eGFR from baselineto on-treatment by ≥20% as measured using either cystatin C or 24h urine collection
Study labs will be obtained within 3-9 weeks after PARPi is initiated

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Within 4 Weeks of Post-discontinuation of PARPi (Time Point C) for patients with clinically significant changes in eGFR based on serum creatinine, cystatin C, or 24 hour urinalysis at Timepoint B
Time Frame: Post-treatment (within 4 weeks of PARP inhibitor discontinuation, only for those patients with clinically significant changes in GFR based on serum creatinine, cystatin C, or 24 hour urinalysis at Timepoint B
The percentage of patients who experience a eGFR reduction of ≥30%, and/or
Post-treatment (within 4 weeks of PARP inhibitor discontinuation, only for those patients with clinically significant changes in GFR based on serum creatinine, cystatin C, or 24 hour urinalysis at Timepoint B

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Investigators

  • Principal Investigator: Payal Shah, MD, University of Pennsylvania

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 3, 2020

Primary Completion (Actual)

July 1, 2021

Study Completion (Actual)

July 1, 2021

Study Registration Dates

First Submitted

April 3, 2020

First Submitted That Met QC Criteria

April 24, 2020

First Posted (Actual)

April 29, 2020

Study Record Updates

Last Update Posted (Actual)

January 26, 2022

Last Update Submitted That Met QC Criteria

January 20, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 829785

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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