Clinical trial NCT04367467: Effect of PARP Inhibitors on Glomerular Filtration Rate
Official title: Effect of PARP Inhibitors on Glomerular Filtration Rate
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Solid Tumor
Ovarian Cancer
Breast Cancer
Keywords: PARPi
Kidney function
Cystatin-C
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2020-04-29
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Change in eGFR from Baseline to On-Treatment, 3-9 weeks after PARPi Initiation (Time Point B)
timeFrame: Study labs will be obtained within 3-9 weeks after PARPi is initiated
Secondary outcomes:
measure: 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
timeFrame: 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 outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Payal Shah, MD
role: PRINCIPAL_INVESTIGATOR
References: