NCT05078671: PROACTIVE

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

Recruiting now Phase 4 Last updated 12 June 2024

What this trial tests

Phase 4 trial testing Olaparib in Cancer in 160 participants. Currently enrolling.

Timeline

15 December 2021

Primary endpoint
31 December 2025

31 December 2025

Quick facts

Lead sponsor	Radboud University Medical Center
Phase	Phase 4
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	160
Start date	15 December 2021
Primary completion	31 December 2025
Estimated completion	31 December 2025
Sites	10 locations across Netherlands

Drugs / interventions tested

• Olaparib (olaparib) — full drug profile →
• Cobicistat (COBICISTAT) — full drug profile →

Conditions studied

• Cancer — all drugs for Cancer →

Sponsor

Radboud University Medical Center

Who can join

18 and older, any sex, with Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Pharmacokinetic Boosting of Kinase Inhibitors.
   Westra N, Touw D, Lub-de Hooge M, Kosterink J, et al · · 2023 · cited 17× · PMID 37111635 · DOI 10.3390/pharmaceutics15041149
2. Off-label, but on target: the evidence needed to implement alternative dosing regimens of anticancer drugs.
   Overbeek JK, Ter Heine R, Verheul HMW, Chatelut E, et al · · 2023 · cited 14× · PMID 36603522 · DOI 10.1016/j.esmoop.2022.100749
3. Pharmacokinetic boosting of olaparib: Study protocol of a multicentre, open-label, randomised, non-inferiority trial (PROACTIVE-B).
   Overbeek JK, Guchelaar NAD, Mohmaed Ali MI, Sark M, et al · · 2025 · cited 2× · PMID 40248173 · DOI 10.1016/j.conctc.2025.101477
4. Population Pharmacokinetics of Cobicistat and its Effect on the Pharmacokinetics of the Anticancer Drug Olaparib.
   Overbeek JK, van Erp NP, Burger DM, den Broeder AA, et al · · 2025 · PMID 39909979 · DOI 10.1007/s40262-025-01480-w