Clinical trial NCT03570476 (phase 2, status: terminated)
Conditions: prostate adenocarcinoma without neuroendocrine differentiation, stage i prostate cancer ajcc v8, stage ii prostate cancer ajcc v8, stage iia prostate cancer ajcc v8, stage iib prostate cancer ajcc v8, stage iic prostate cancer ajcc v8
ICD codes: C22.0, C22.1, C4A.9, C7B.1, D09.9, C4A.0, C4A.31, C61, D29.1, D40.0, Z15.03, Z80.42, Z85.46, Z12.5, C61, D29.1, D40.0, Z15.03, Z80.42, Z85.46, Z12.5, C61, D29.1, D40.0, Z15.03, Z80.42, Z85.46, Z12.5, C61, D29.1, D40.0, Z15.03, Z80.42, Z85.46, Z12.5, C61, D29.1, D40.0, Z15.03, Z80.42, Z85.46, Z12.5
Drugs: olaparib
SMILES: OC1=NN=C(CC2=CC(C(=O)N3CCN(CC3)C(=O)C3CC3)=C(F)C=C2)C2=CC=CC=C12
Reason stopped: 
    terminated due to slow accrual
  
Eligibility criteria:

        Inclusion Criteria:

          -  Provision of informed consent prior to any study specific procedures.

          -  Histologically confirmed adenocarcinoma of the prostate without morphologic
             neuroendocrine differentiation or small cell features.

          -  The presence of homologous recombination deficiency defined by either; A) Inherited
             pathogenic variant of BRCA2, ATM, BRCA1, PALB2 by a Clinical Laboratory Improvement
             Act (CLIA) level germline assay or B) have evidence by somatic sequencing using a CLIA
             level assay of biallelic inactivation of BRCA1, BRCA2, PALB2, FANCA or biallelic
             inactivation or monoallelic inactivating mutation of ATM. It is anticipated that the
             majority of patients will be germline carriers of a pathogenic variant of BRCA1, BRCA2
             or ATM. Other germline mutations will be considered at investigator's discretion.

          -  Must be candidates for radical prostatectomy and considered surgically resectable by
             urologic evaluation.

          -  No evidence of metastatic disease or nodal disease as determined by radionuclide bone
             scans and computed tomography (CT)/magnetic resonance imaging (MRI); non-pathological
             lymph nodes must be less than 20 mm in the short (transverse) axis.

          -  Provided written authorization for use and release of health and research study
             information.

          -  Hemoglobin >= 10.0 g/dL with no blood transfusion in the past 28 days.

          -  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 using the Cockcroft-Gault equation
             of >= 51 mL/min (within 28 days prior to administration of study treatment).

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

          -  Patients must have a life expectancy >= 16 weeks.

          -  Male patients and their partners, who are sexually active and of childbearing
             potential, must agree to the use of two highly effective forms of contraception in
             combination throughout the period of taking study treatment and for 3 months after
             last dose of study drug(s) to prevent pregnancy in a partner.

          -  Patient is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations.

        Exclusion Criteria:

          -  Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             staff and/or staff at the study site).

          -  Any previous treatment with PARP inhibitor, including olaparib.

          -  Other malignancy within the last 5 years except: adequately treated non-melanoma skin
             cancer, or other solid tumors including lymphomas (without bone marrow involvement)
             curatively treated with no evidence of disease for >= 5 years.

          -  Resting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec on 2 or
             more time points within a 24-hour period or family history of long QT syndrome.

          -  Patients receiving any systemic chemotherapy, hormonal therapy or radiotherapy.

          -  Concomitant use of known strong CYP3A inhibitors (e.g. 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, 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 phenobarbital and 3 weeks for other agents.

          -  Patients with myelodysplastic syndrome/acute myeloid leukemia or with features
             suggestive of myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML).

          -  Major surgery within 2 weeks of starting study treatment and patients must have
             recovered from any effects of any major surgery.

          -  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, 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).

          -  Patients with a known hypersensitivity to olaparib or any of the excipients of the
             product.

          -  Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of
             transmitting the infection through blood or other body fluids.

          -  Previous allogenic bone marrow transplant or cord blood transplantation.

          -  Whole blood transfusions in the last 120 days prior to entry to the study (packed red
             blood cells and platelet transfusions are acceptable).