CancerPhase 4PROACTIVENCT05078671
Pharmacokinetic Boosting of Olaparib to Improve Exposure, Tolerance and Cost-effectiveness
A Phase 4 study testing Olaparib and Cobicistat in people with Cancer, run by Radboud University Medical Center at 10 sites in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- Olaparib and Cobicistat
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 10 sitesNetherlands
- Study dates
- 15 Dec 2021to 31 Dec 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- Concurrent use of other anti-cancer therapies;
- Concurrent use of potent inducers or inhibitors of the cytochrome p450 enzyme 3A3 (CYP3A4) as assessed with the Dutch drug database "G-Standaard" of the Royal Dutch Pharmacists Association(KNMP);
- Known contra-indications for treatment with cobicistat in line with the summary of product characteristics;
- Subjects with renal insufficiency defined as estimated glomerular filtration rate < 50 ml/min.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Netherlands10 sites, 10 recruiting
- Recruiting
Jeroen Bosch Ziekenhuis
's-Hertogenbosch
J. Tol
- Recruiting
Amsterdam Universitair Medische Centra
Amsterdam
J.M. Tromp
- Recruiting
Netherlands Cancer Institute-Antoni van Leeuwenhoek
Amsterdam
Frans Opdam, MD, PharmD, PhD
- Recruiting
Amphia Ziekenhuis
Breda
J. Bakker
- Recruiting
Universitair Medisch Centrum Groningen
Groningen
A.K.L. Reyners
- Recruiting
Leiden University Medical Center
Leiden
J.R. Kroep
- Recruiting
Maastricht UMC
Maastricht
R.I. Lalisang
- Recruiting
Radboudumc
Nijmegen
Nielka van Erp, prof. PharmD PhD
- Recruiting
ErasmusMC
Rotterdam
Ron H.J. Mathijssen, prof. MD, PhD
- Recruiting
Universitair Medisch Centrum Utrecht
Utrecht
I.O. Baas
About this study
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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaparibDrug
olaparib treatment
CobicistatDrug
Pharmacokinetic booster
| Study group | Role | What they receive |
|---|---|---|
| Standard olaparib | Active comparator | Olaparib 300mg twice daily Receives: Drug: Olaparib |
| Boosted olaparib | Experimental | Olaparib 100mg twice daily + cobicistat 150mg twice daily Receives: Drug: Olaparib; Drug: Cobicistat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Olaparib AUC0-12h
The Area-Under-the-Curve (AUC) 0-12h of olaparib.
Measured: 2 weeks
Part B: Progression-free survival (PFS)
PFS is defined as time from randomization until the date of either objective radiological disease progression, or biochemical progression combined with clinical progression or death.
Measured: 12 months
Part B: Dose reductions
Number of patients who require a dose reduction due to toxicity.
Measured: 12 months
Secondary outcomes (8)
Part A: Inter- and intrapatient variability of AUC0-12h
Inter- and intrapatient variability of AUC0-12h in olaparib as calculated with non-compartmental analysis.
Measured: 2 weeks
Part A: Adverse events
Number of patients with treatment-related adverse events as assessed by CTCAE v5.0.
Measured: 2 weeks
Part B: Health status
Health status as assessed with the EuroQol 5 dimensions with 5 levels questionnaire (EQ-5D-5L).
Measured: 12 months
Part B: Patient satisfaction
Patient satisfaction as assessed with the Cancer Therapy Satisfaction Questionnaire (CTSQ).
Measured: 12 months
Part B: ctDNA
Cell-free tumor nucleic acids (ctDNA) in plasma as pharmacodynamic biomarker.
Measured: 12 weeks
Part B: Adverse events
Number of patients with treatment-related adverse events as assessed by CTCAE v5.0.
Measured: 12 months
Part B: Productivity costs
Productivity costs as assessed by the iMTA Productivity Costs Questionnaire (iPCQ).
Measured: From date of randomization until the date of end-of-treatment, assessed up to 12 months
Part B: Medical consumption
Medical consumption as assessed by the iMTA Medical Consumption Questionnaire (iMCQ).
Measured: From date of randomization until the date of end-of-treatment, assessed up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2021
- Study start15 Dec 2021
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Part A: cross-over normal olaparib versus boosted olaparib. Part B: normal olaparib versus boosted olaparib in two patient groups.
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nielka van Erp, prof. PharmD PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05078671
- Sponsor's protocol ID
- PROACTIVE
- Acronym
- PROACTIVE
- Status last verified
- Jun 2024
- First submitted
- 22 Sep 2021
- Last updated
- 12 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Overbeek JK, Guchelaar NAD, Mohmaed Ali MI, Ottevanger PB, Bloemendal HJ, Koolen SLW, Mathijssen RHJ, Boere IA, Hamberg P, Huitema ADR, Sonke GS, Opdam FL, Ter Heine R, van Erp NP. Pharmacokinetic boosting of olaparib: A randomised, cross-over study (PROACTIVE-study). Eur J Cancer. 2023 Nov;194:113346. doi: 10.1016/j.ejca.2023.113346. Epub 2023 Sep 19.
PubMed 37806255Overbeek JK, Guchelaar NAD, Mohmaed Ali MI, Sark M, Hovenier C, Kievit W, Ligtenberg MJL, Ottevanger PB, Bloemendal HJ, Koolen SLW, Mathijssen RHJ, Boere IA, Huitema ADR, Sonke GS, Opdam FL, Ter Heine R, van Erp NP. Pharmacokinetic boosting of olaparib: Study protocol of a multicentre, open-label, randomised, non-inferiority trial (PROACTIVE-B). Contemp Clin Trials Commun. 2025 Mar 29;45:101477. doi: 10.1016/j.conctc.2025.101477. eCollection 2025 Jun.
PubMed 40248173Overbeek JK, van Erp NP, Burger DM, den Broeder AA, Koolen SLW, Huitema ADR, Ter Heine R. Population Pharmacokinetics of Cobicistat and its Effect on the Pharmacokinetics of the Anticancer Drug Olaparib. Clin Pharmacokinet. 2025 Mar;64(3):425-435. doi: 10.1007/s40262-025-01480-w. Epub 2025 Feb 5.
PubMed 39909979
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Boosting of Olaparib to Improve Exposure, Tolerance and Cost-effectiveness
- ClinicalTrials.gov ID
- NCT05078671
- Acronym / sponsor ID
- PROACTIVE / PROACTIVE
- Conditions
- Cancer
- Keywords
- olaparib, pharmacokinetic enhancement
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 15 Dec 2021 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 14 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Part A: cross-over normal olaparib versus boosted olaparib. Part B: normal olaparib versus boosted olaparib in two patient groups.
| Arm | Type | Receives |
|---|---|---|
| Standard olaparib | Active comparator | Drug: OlaparibOlaparib 300mg twice daily |
| Boosted olaparib | Experimental | Drug: Olaparib, Drug: CobicistatOlaparib 100mg twice daily + cobicistat 150mg twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
- 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.
Key exclusion criteria (4 listed)
- Concurrent use of other anti-cancer therapies;
- Concurrent use of potent inducers or inhibitors of the cytochrome p450 enzyme 3A3 (CYP3A4) as assessed with the Dutch drug database "G-Standaard" of the Royal Dutch Pharmacists Association(KNMP);
- Known contra-indications for treatment with cobicistat in line with the summary of product characteristics;
- Subjects with renal insufficiency defined as estimated glomerular filtration rate < 50 ml/min.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Olaparibolaparib treatment | Drug | Boosted olaparib, Standard olaparib |
| CobicistatPharmacokinetic booster | Drug | Boosted olaparib |
Primary outcome
Part A: Olaparib AUC0-12h
Time frame: 2 weeks
The Area-Under-the-Curve (AUC) 0-12h of olaparib.
Part B: Progression-free survival (PFS)
Time frame: 12 months
PFS is defined as time from randomization until the date of either objective radiological disease progression, or biochemical progression combined with clinical progression or death.
Part B: Dose reductions
Time frame: 12 months
Number of patients who require a dose reduction due to toxicity.
8 secondary outcomes
Part A: Inter- and intrapatient variability of AUC0-12h
Time frame: 2 weeks
Part A: Adverse events
Time frame: 2 weeks
Part B: Health status
Time frame: 12 months
Part B: Patient satisfaction
Time frame: 12 months
Part B: ctDNA
Time frame: 12 weeks
Part B: Adverse events
Time frame: 12 months
Part B: Productivity costs
Time frame: From date of randomization until the date of end-of-treatment, assessed up to 12 months
Part B: Medical consumption
Time frame: From date of randomization until the date of end-of-treatment, assessed up to 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2024.
- Results publication: PubMed 37806255Overbeek JK, Guchelaar NAD, Mohmaed Ali MI, Ottevanger PB, Bloemendal HJ, Koolen SLW, Mathijssen RHJ, Boere IA, Hamberg P, Huitema ADR, Sonke GS, Opdam FL, Ter Heine R, van Erp NP. Pharmacokinetic boosting of olaparib: A randomised, cross-over study (PROACTIVE-study). Eur J Cancer. 2023 Nov;194:113346. doi: 10.1016/j.ejca.2023.113346. Epub 2023 Sep 19.
- Derived from this study: PubMed 40248173Overbeek JK, Guchelaar NAD, Mohmaed Ali MI, Sark M, Hovenier C, Kievit W, Ligtenberg MJL, Ottevanger PB, Bloemendal HJ, Koolen SLW, Mathijssen RHJ, Boere IA, Huitema ADR, Sonke GS, Opdam FL, Ter Heine R, van Erp NP. Pharmacokinetic boosting of olaparib: Study protocol of a multicentre, open-label, randomised, non-inferiority trial (PROACTIVE-B). Contemp Clin Trials Commun. 2025 Mar 29;45:101477. doi: 10.1016/j.conctc.2025.101477. eCollection 2025 Jun.
- Derived from this study: PubMed 39909979Overbeek JK, van Erp NP, Burger DM, den Broeder AA, Koolen SLW, Huitema ADR, Ter Heine R. Population Pharmacokinetics of Cobicistat and its Effect on the Pharmacokinetics of the Anticancer Drug Olaparib. Clin Pharmacokinet. 2025 Mar;64(3):425-435. doi: 10.1007/s40262-025-01480-w. Epub 2025 Feb 5.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nielka van Erp, prof. PharmD PhD principal investigator
Radboud University Medical Center
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Olaparib and Cobicistat in people with Cancer, run by Radboud University Medical Center at 10 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Joanneke K Overbeek, PharmD (+31-24-3617744, joanneke.overbeek@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Olaparib AUC0-12h (time frame: 2 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05078671, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2024.