| Eligibility |
Inclusion Criteria:
- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol
- Subject must be >= 18 years of age at the time of signing the informed consent form
- Individuals who have documented histologically confirmed adenocarcinoma of the
prostate
- Subject must have evidence of castration resistant prostate cancer as evidenced by PSA
progression (per Prostate Cancer Working Group 3 [PCWG3] criteria) and a castrate
serum testosterone level (i.e. =< 50 mg/dL)
- PSA must be at least 2 ng/mL and rising on two successive measurements at least two
weeks apart
- At least one lesion (measurable and/or non-measurable) that can be accurately assessed
at baseline by computed tomography (CT) scan, magnetic resonance imaging (MRI), or
positron emission tomography (PET) and is suitable for repeated assessment
- Must have progressed on abiraterone and/or a second-generation androgen receptor (AR)
antagonist (i.e. enzalutamide, apalutamide, or darolutamide). If these were given in
the hormone sensitive setting, patients must also have progressed on at least one
prior approved therapy for CRPC
- Must have archival tissue available or be willing to undergo metastatic biopsy in
order to perform next-generation deoxyribonucleic acid (DNA) sequencing and undergo
whole exome sequencing
- Patient must have a positive LOH score on prior University of Washington (UW) OncoPlex
testing
- Hemoglobin >= 10.0 g/dL with no blood transfusion in the past 28 days (within 28 days
prior to administration of study treatment)
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 28 days prior to
administration of study treatment)
- Platelet count >= 100 x 10^9/L (within 28 days prior to administration of study
treatment)
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 28 days
prior to administration of study treatment)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal unless liver metastases are present in
which case they must be =< 5 x ULN (within 28 days prior to administration of study
treatment)
- Patients must have creatinine clearance estimated of >= 51 mL/min using the
Cockcroft-Gault equation or based on a 24 hour urine test (within 28 days prior to
administration of study treatment)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients must have an estimated life expectancy >= 16 weeks
- Male patients must use a condom during treatment and for 3 months after the last dose
of olaparib 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:
- As judged by the investigator, any evidence of serious and/or unstable pre-existing
medical or psychiatric condition which in the investigator's opinion makes it
undesirable for the patient to participate in the trial
- Other malignancy unless curatively treated with no evidence of disease for >= 5 years
except: adequately treated non-melanoma skin cancer and non-muscle invasive bladder
cancer
- Resting electrocardiography (ECG) indicating uncontrolled, potentially reversible
cardiac conditions, as judged by the investigator (e.g., unstable ischemia,
uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval
by Fridericia's formula [QTcF] prolongation > 500 ms, electrolyte disturbances, etc.),
or patients with congenital long QT syndrome
- Persistent toxicities (> Common Terminology Criteria for Adverse Event (CTCAE) grade
2) caused by previous cancer therapy, excluding alopecia
- Patients with myelodysplastic syndrome/acute myeloid leukemia or with features
suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
- Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence
of brain metastases is not required. The patient can receive a stable dose of
corticosteroids before and during the study as long as these were started at least 4
weeks prior to treatment. Patients with spinal cord compression unless considered to
have received definitive treatment for this and evidence of clinically stable disease
for 28 days
- Patients considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection. Examples
include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3
months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal
cord compression, superior vena cava syndrome, extensive interstitial bilateral lung
disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder
that prohibits obtaining informed consent
- Patients unable to swallow orally administered medication and patients with
gastrointestinal disorders likely to interfere with absorption of the study medication
- Immunocompromised patients, e.g., patients who are known to be serologically positive
for human immunodeficiency virus (HIV) and are not receiving active treatment or have
a detectable viral load
- Patients with known active hepatitis (i.e. hepatitis B or C).
- Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen
(HBsAg) result. Patients with a past or resolved HBV infection (defined as the
presence of hepatitis B core antibody and absence of HBsAg) are eligible
- Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
- Any previous treatment with PARP inhibitor, including olaparib
- Any previous treatment with platinum chemotherapy in the metastatic
castration-resistant setting
- Patients receiving any systemic chemotherapy or radiotherapy (except for palliative
reasons) within 3 weeks prior to study treatment
- Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin,
clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g.
ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout
period prior to starting olaparib is 2 weeks
- Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin,
rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort ) or
moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout
period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital 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)
- Patients with a known hypersensitivity to olaparib or any of the excipients of the
product
- Involvement in the planning and/or conduct of the study
- 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
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