Pharmacokinetic Boosting of Olaparib to Improve Exposure, Tolerance and Cost-effectiveness

Who is this study for? Patients with Cancer
What treatments are being studied? Olaparib
Status: Recruiting
Location: See all (10) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 4
SUMMARY

Olaparib is a poly-adenosine diphosphate ribose polymerase (PARP) inhibitor, originally used for the maintenance treatment of women with platinum-sensitive relapsed breast cancer gene (BRCA)-mutated high grade serious epithelial ovarian, fallopian tube, or peritoneal cancer, who are in response to platinum-based chemotherapy. Over the last two years, several therapeutic indications have been added to the drug label, such as first-line platinum-sensitive BRCA-mutated high grade serious epithelial ovarian, fallopian tube, or peritoneal cancer, germline BRCA1/2-mutated, human epidermal growth factor 2 (HER2-)negative, locally advanced or metastatic breast cancer and BRCA1/2-mutated metastatic castration-resistant prostate cancer, who have progressed following prior therapy. Since olaparib is very expensive, this increase of treatment population will have a significant impact on health care expenditures. To keep healthcare affordable and accessible for all patients, innovative strategies are warranted to reduce the dose of expensive drugs, without reduction of efficacy. For olaparib, pharmacokinetic (PK) boosting can be applied. PK boosting is the lay term for administering a non-therapeutic active strong inhibitor of a metabolic enzyme, for example the cytochrome p450 enzyme 3A (CYP3A), together with a therapeutic drug that is metabolized by the same enzyme. Boosting thus increases the concentration of the therapeutic drug and allows lower doses to be administered to patients. Hence, coadministration of a reduced dose of olaparib with cobicistat, a non-therapeutic, strong inhibitor of the CYP3A can lead to equivalent exposure to olaparib. Furthermore, inhibition of CYP3A could lead to less PK variability since metabolic capacity is a prominent cause for (intra- and inter-individual) variability in systemic exposure. Predictable olaparib exposure will reduce the number of patients who are unintentionally under- or overtreated. Lastly, tumor tissue itself may express CYP3A as a detoxification or resistance mechanism. Theoretically, PK boosting may also overcome CYP3A-mediated drug resistance. The purpose of this study is to establish the efficacy, safety and feasibility of co-administering olaparib with the PK booster cobicistat with the aim to implement boosting approach for olaparib in routine practice. The study is subdivided in two parts. In part A of the study the equivalent exposure of boosted low dose olaparib is determined compared to the normal dose. In part B of the study, non-inferiority of the boosted olaparib regimen will be confirmed.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Subjects who are able and willing to provide written informed consent prior to screening;

• Age of 18 years or older;

• Able to measure the outcome of the study in this subject.

⁃ Part A:

• Subjects who start or are on treatment with olaparib tablets 300mg twice daily, according to the drug label and physician's discretion;

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

⁃ Part B:

• Subjects who start on treatment with olaparib tablets 300mg twice daily, according to the drug label and physician's discretion;

• Expected to be on olaparib treatment for ≥ 3 months;

• ECOG performance status of 0-3.

Locations
Other Locations
Netherlands
Jeroen Bosch Ziekenhuis
RECRUITING
's-hertogenbosch
Amsterdam Universitair Medische Centra
RECRUITING
Amsterdam
Netherlands Cancer Institute-Antoni van Leeuwenhoek
RECRUITING
Amsterdam
Amphia Ziekenhuis
RECRUITING
Breda
Universitair Medisch Centrum Groningen
RECRUITING
Groningen
Leiden University Medical Center
RECRUITING
Leiden
Maastricht UMC
RECRUITING
Maastricht
Radboudumc
RECRUITING
Nijmegen
ErasmusMC
RECRUITING
Rotterdam
Universitair Medisch Centrum Utrecht
RECRUITING
Utrecht
Contact Information
Primary
Joanneke K Overbeek, PharmD
joanneke.overbeek@radboudumc.nl
+31-24-3617744
Time Frame
Start Date: 2021-12-15
Estimated Completion Date: 2025-12-31
Participants
Target number of participants: 160
Treatments
Active_comparator: Standard olaparib
Olaparib 300mg twice daily
Experimental: Boosted olaparib
Olaparib 100mg twice daily + cobicistat 150mg twice daily
Related Therapeutic Areas
Sponsors
Leads: Radboud University Medical Center

This content was sourced from clinicaltrials.gov

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