To determine the influence of darolutamide on the pharmacokinetics of cabazitaxel compared to cabazitaxel alone in mCRPC patients.
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
In this exploratory study, the influence of darolutamide on the
pharmacokinetics of cabazitaxel will be determined. Each patient will be its
own control. The primary study endpoint is the Area Under the plasma
concentration time Curve (AUC) of cabazitaxel, where a comparison will be made
between the AUC of cabazitaxel monotherapy and the AUC of cabazitaxel with
darolutamide.
Secondary outcome
1. To evaluate the efficacy of cabazitaxel and darolutamide combination
therapy, by means of PSA response, compared to baseline.
2. To study the pharmacokinetic profile of darolutamide.
3. To evaluate the safety of cabazitaxel and darolutamide combination therapy.
Background summary
Darolutamide (Nubeqa) is a novel androgen receptor antagonist drug for the
treatment of non-metastatic castration resistant prostate cancer (CRPC),
approved by the FDA and EMA. It does not inhibit major CYP enzymes or major
transporters at clinically relevant concentrations, so it is thought to be less
sensitive for drug-drug interactions (DDIs), compared to other agents. Several
clinical studies investigating the efficacy of combining hormonal therapy, like
androgen receptor antagonists, with chemotherapy in metastatic CRPC patients
are ongoing and the first data are promising. However, due to DDIs between
these agents, which likely affect the anti-tumor activity of the treatment,
there is a need for testing new, potentially more effective chemo-hormonal
combination regimens. Since darolutamide is likely to cause fewer DDIs in the
clinical setting and also possesses several advantages over other androgen
receptor targeted agents (ARTAs), the combination of cabazitaxel and
darolutamide might yield superior anti-tumor activity. In this exploratory
study we will therefore evaluate the extent by which cabazitaxel exposure is
affected by concomitant use of darolutamide in metastatic CRPC patients.
Study objective
To determine the influence of darolutamide on the pharmacokinetics of
cabazitaxel compared to cabazitaxel alone in mCRPC patients.
Study design
This is an open label single arm pharmacokinetic drug-drug interaction study.
Intervention
Patients will start on day 1 with cabazitaxel, which will be administered once
every 3 weeks (one cycle) in 20 mg/m2, according to standard of care.
Darolutamide 600 mg b.i.d. will be added on day 2 for 12 weeks. Patients will
be admitted to the hospital for pharmacokinetic blood sampling at day 1 of
cycle 1 and day 1 of cycle 3 (day 43). There is an optional pharmacokinetic
blood sampling at day 1 of cycle 5 (day 85).
Study burden and risks
Patients on regular treatment with cabazitaxel will be admitted to the hospital
on 2 different days. Cabazitaxel (20 mg/m2, IV) will be administered and
pharmacokinetic blood withdrawals will be performed. The day after the first
hospital admission, patients will start with darolutamide for 12 weeks (600 mg
b.i.d., PO). Patients could benefit individually from this study, as
combination treatment might exert superior anti-tumor activity. Major risks to
be expected are side effects of one of the medicinal products cabazitaxel or
darolutamide, for which patients will be carefully observed.
Dr. Molewaterplein 40
Rotterdam 3015GD
NL
Dr. Molewaterplein 40
Rotterdam 3015GD
NL
Listed location countries
Age
Inclusion criteria
1. Age * 18 years;
2. Patients with a confirmed diagnosis of mCRPC with an indication for
cabazitaxel treatment at the standard dose of 20 mg/m2.
3. WHO performance * 1.
4. Able and willing to sign the Informed Consent Form prior to screening
evaluations
5. Adequate baseline patient characteristics (complete blood count, serum
biochemistry which involves sodium, potassium, creatinine, calculation of
creatinine clearance, AST, ALT, gamma glutamyltranspeptidase, lactate
dehydrogenase, ALP, Total bilirubin, Albumin, glucose)
Exclusion criteria
1. Use of (over the counter) medication or (herbal) supplements which can
interact with either cabazitaxel or darolutamide, e.g. by induction or
inhibition of CYP3A4 or P-gp. Dexamethasone and prednisone are allowed.
2. Patients with known impaired drug absorption (e.g. gastrectomy and
achlorhydria)
3. Known serious illness or medical unstable conditions that could interfere
with this study requiring treatment (e.g. HIV, hepatitis, Varicella zoster or
herpes zoster, organ transplants, kidney failure (GFR<60), serious liver
disease (e.g. severe cirrhosis), cardiac and respiratory diseases)
4. Treatment with abiraterone, enzalutamide, apalutamide or darolutamide six
weeks prior to day 1 of the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-000823-38-NL |
| CCMO | NL73182.056.20 |
| OMON | NL-OMON28448 |