Study on Olaparib Plus Abiraterone as First-line Therapy in Men With Metastatic Castration-resistant Prostate Cancer

  • STATUS
    Recruiting
  • End date
    Apr 28, 2026
  • participants needed
    904
  • sponsor
    AstraZeneca
Updated on 19 August 2021
Investigator
AstraZeneca Clinical Study Information Center
Primary Contact
Research Site (0.8 mi away) Contact
+197 other location
ct scan
MRI
testosterone
progressive disease
androgen suppression
abiraterone
serum testosterone
gonadotropin releasing hormone
androgen
adenocarcinoma
olaparib
prostate adenocarcinoma

Summary

The purpose of this study is to evaluate the efficacy and safety (including evaluating side effects) of combination of olaparib and abiraterone versus placebo and abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) who have received no prior cytotoxic chemotherapy or new hormonal agents (NHAs) at metastatic castration-resistant prostate cancer (mCRPC) stage.

Description

PROpel is a phase III study evaluating the efficacy, safety, and tolerability of olaparib versus placebo when given in addition to abiraterone to patients with metastatic castration-resistant prostate cancer (mCRPC) who have not received prior chemotherapy or new hormonal agents (NHAs) for metastatic castration-resistant prostate cancer (mCRPC) (first-line setting).

Approximately 720 patients globally were planned to be randomized in PROpel in a 1:1 ratio to treatment with either olaparib and abiraterone or placebo and abiraterone. Enrolment had completed with a total of 796 patients randomised. Following the completion of global enrolment, the China cohort will randomise approximately 108 additional patients at sites in China, also in a 1:1 ratio.

Patients will receive oral treatment with olaparib 300 mg twice daily + abiraterone 1000 mg once daily or placebo twice daily + abiraterone 1000 mg once daily. Patients in both treatment groups will also receive either prednisone or prednisolone 5 mg twice daily.

Details
Condition Metastatic Castration Resistant Prostate Cancer
Treatment olaparib, abiraterone acetate
Clinical Study IdentifierNCT03732820
SponsorAstraZeneca
Last Modified on19 August 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in the study protocol
Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses
For inclusion in i) the optional exploratory genetic research and ii) the optional biomarker research, patients must fulfill the following criteria
Provision of informed consent for genetic research prior to collection of sample
Provision of informed consent for biomarker research prior to collection of sample
If a patient declines to participate in the optional exploratory genetic
research or the optional biomarker research, there will be no penalty or loss
of benefit to the patient. The patient will not be excluded from other aspects
of the study
\. Patients must be 18 years of age (or 19 years of age in South Korea) at
the time of signing the informed consent form. For patients enrolled in Japan
who are <20 years of age, written informed consent should be obtained from the
patient and from his legally acceptable representative
\. Histologically or cytologically confirmed prostate adenocarcinoma
\. Metastatic status defined as at least 1 documented metastatic lesion on
either a bone scan or a computed tomography(CT)/ magnetic resonance imaging
(MRI) scan
\. First-line metastatic castration-resistant prostate cancer (mCRPC)
\. Ongoing androgen deprivation with gonadotropin-releasing hormone analogue
or bilateral orchiectomy, with serum testosterone <50 nanograms per decilitre
(ng/dL) (<2.0 nanomoles per litre (nmol/L)) within 28 days before
randomisation. Patients receiving androgen deprivation therapy (ADT) at study
entry should continue to do so throughout the study
\. Candidate for abiraterone therapy with documented evidence of progressive
disease
\. Patients must have normal organ and bone marrow function measured within
days prior to administration of study treatment
\. Eastern Cooperative Oncology Group (ECOG) performance status 0-1, with no
deterioration over the previous 2 weeks
\. The participant has, in the opinion of the investigator, a life
expectancy of at least 6 months
\. Prior to randomisation, sites must confirm availability of either an
archival formalin fixed, paraffin embedded (FFPE) tumour tissue sample, or a
new biopsy taken during the screening window, which meets the minimum
pathology and sample requirements in order to enable homologous recombination
repair (HRR) status subgroup analysis of the primary endpoint radiographic
progression-free survival (rPFS). If there is not written confirmation of the
availability of tumour tissue prior to randomisation, the patient is not
eligible for the study
\. Male patients must use a condom during treatment and for 3 months after
the last dose of olaparib+abiraterone when having sexual intercourse with a
pregnant woman or with a woman of childbearing potential. Female partners of
male patients should also use a highly effective form of contraception if they
are of childbearing potential

Exclusion Criteria

Has a known additional malignancy that has had progression or has required active treatment in the last 5 years
Patients with myelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML) or with features suggestive of yelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML)
Clinically significant cardiovascular disease Association Class II-IV heart failure or cardiac ejection fraction measurement of <50% during screening as assessed by echocardiography or multigated acquisition scan
Planned or scheduled cardiac surgery or percutaneous coronary intervention procedure
Prior revascularisation procedure (significant coronary, carotid, or peripheral artery stenosis)
Uncontrolled hypertension (systolic blood pressure (BP) 160 millimeters of mercury (mmHg) or diastolic blood pressure (BP) 95 millimeters of mercury (mmHg))
History of uncontrolled pituitary or adrenal dysfunction
Active infection or other medical condition that would make prednisone/prednisolone use contraindicated
Any chronic medical condition requiring a systemic dose of corticosteroid >10 milligrams (mg) prednisone/prednisolone per day
Patients who are considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection
Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAEs] grade >2) caused by previous cancer therapy, excluding alopecia
Patients with brain metastases. A scan to confirm the absence of brain metastases is not required
Patients with spinal cord compression are excluded unless they are considered to have received definitive treatment for this and have evidence of clinically stable disease for 4 weeks
Patients who are unevaluable for both bone and soft tissue progression
Patients who are unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
Immunocompromised patients
Patients with known active hepatitis infection (ie, hepatitis B or C)
Any previous treatment with Polyadenosine 5'diphosphoribose [poly (ADP ribose)] polymerase (PARP) inhibitor, including olaparib
Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment. Patients who receive palliative radiotherapy need to stop radiotherapy 1 week before randomisation
Any previous exposure to a Cytochrome P450 (CYP) 17 (17-hydroxylase/C17,20-lyase) inhibitor (eg, abiraterone, orteronel)
Concomitant use of known strong Cytochrome P450 (CYP) 3A inhibitors (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks
Concomitant use of known strong Cytochrome P450 (CYP) 3A inducers (eg, phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine or St John's wort) or moderate Cytochrome P450 (CYP) 3A inducers (eg, bosentan, efavirenz or modafinil). The required period prior to starting study treatment is 5 weeks for phenobarbital and enzalutamide and 3 weeks for other agents
Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
Participation in another clinical study with an investigational product or investigational medical devices within 1 month of randomisation
History of hypersensitivity to olaparib or abiraterone, any of the excipients of olaparib or abiraterone, or drugs with a similar chemical structure or class to olaparib or abiraterone
Involvement in the planning and/or conduct of the study (applies to both AstraZeneca and Merck staff and/or staff at the study site)
Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
Previous randomisation in the present study
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note