Effect of PARP Inhibitors on Glomerular Filtration Rate

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Terminated
• CT.gov ID: NCT04367467
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Actual Duration (Months): 16.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor; Ovarian Cancer; Breast Cancer	Other: Kidney Function Test

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 Design

• Study Type: Observational
• Actual Enrollment: 2 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Effect of PARP Inhibitors on Glomerular Filtration Rate
• Actual Study Start Date: Feb 3, 2020
• Actual Primary Completion Date: Jul 1, 2021
• Actual Study Completion Date: Jul 1, 2021

Arms and Interventions

Arm

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

Outcome Measures

Primary Outcome Measures

1. Change in eGFR from Baseline to On-Treatment, 3-9 weeks after PARPi Initiation (Time Point B) [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

Secondary Outcome Measures

1. 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 [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT04367467
• Other Study ID Numbers: 829785
• First Posted: Apr 29, 2020
• Last Update Posted: Jan 26, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Pennsylvania: PARPi; Kidney function; Cystatin-C

Study Results

No Results Posted as of Jan 26, 2022