A Phase 4 interventional study of Olaparib and Cobicistat in Cancer, sponsored by Radboud University Medical Center. Recruiting at 10 sites in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-06-12.
Sponsored by Radboud University Medical Center · Phase 4, Interventional, and Treatment
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.
Radboud University Medical Center is the lead sponsor of 959 studies on the registry; 134 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
Counted across the registry records on this site, refreshed daily.
Part A:
Part B:
Exclusion Criteria:
Olaparib 300mg twice daily
Drug: Olaparib
Olaparib 100mg twice daily + cobicistat 150mg twice daily
Drug: Olaparib · Drug: Cobicistat
olaparib treatment
Pharmacokinetic booster
Part A: Olaparib AUC0-12h
The Area-Under-the-Curve (AUC) 0-12h of olaparib.
Time frame: 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.
Time frame: 12 months
Part B: Dose reductions
Number of patients who require a dose reduction due to toxicity.
Time frame: 12 months
Part A: Inter- and intrapatient variability of AUC0-12h
Inter- and intrapatient variability of AUC0-12h in olaparib as calculated with non-compartmental analysis.
Time frame: 2 weeks
Part A: Adverse events
Number of patients with treatment-related adverse events as assessed by CTCAE v5.0.
Time frame: 2 weeks
Part B: Health status
Health status as assessed with the EuroQol 5 dimensions with 5 levels questionnaire (EQ-5D-5L).
Time frame: 12 months
Part B: Patient satisfaction
Patient satisfaction as assessed with the Cancer Therapy Satisfaction Questionnaire (CTSQ).
Time frame: 12 months
Part B: ctDNA
Cell-free tumor nucleic acids (ctDNA) in plasma as pharmacodynamic biomarker.
Time frame: 12 weeks
Part B: Adverse events
Number of patients with treatment-related adverse events as assessed by CTCAE v5.0.
Time frame: 12 months
Part B: Productivity costs
Productivity costs as assessed by the iMTA Productivity Costs Questionnaire (iPCQ).
Time frame: 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).
Time frame: From date of randomization until the date of end-of-treatment, assessed up to 12 months
Part A: Patient preference
Treatment preference on a 7-point Likert scale.
Time frame: 2 weeks
Part B: Intratumoral olaparib
Intratumoral olaparib concentration in tumor biopsy samples.
Time frame: At 8 weeks after start treatment and at the moment of progression
Plan to share: Undecided
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Radboud University Medical Center