| Eligibility |
Inclusion Criteria:
- Written informed consent and any locally-required authorization (e.g., Health
Insurance Portability and Accountability Act [HIPAA] in the United States of America
[USA]) obtained from the subject prior to performing any protocol-related procedures,
including screening evaluations
- Histology showing high-grade epithelial non-mucinous ovarian, primary peritoneal, or
fallopian tube cancer
- Documented BRCA pathway mutations
- No prior treatment for primary advanced (stage III or IV) epithelial ovarian, primary
peritoneal, or fallopian tube carcinoma such as irradiation, chemotherapy, hormonal
therapy, immunotherapy, investigational therapy, surgery, and/or other concurrent
agents or therapies
- A disposition to neoadjuvant chemotherapy (NACT) with planned interval tumor reductive
surgery after 3 complete cycles of treatment
- Have measurable disease based on RECIST version 1.1 or evaluable disease. Measurable
disease is defined at least one lesion that can be accurately measured in at least one
dimension (longest dimension to be recorded). Each "target" lesion must be > 20 mm
when measured by conventional techniques, including palpation, plain x-ray, computed
tomography (CT), and magnetic resonance imaging (MRI), or > 10 mm when measured by
spiral CT. Evaluable disease includes nonmeasurable lesions, ascites, pleural effusion
- Peripheral neuropathy grade 0 or 1 by Common Terminology Criteria for Adverse Events
(CTCAE) version (v)5.0
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy of >= 16 weeks
- Postmenopausal or evidence of non-childbearing status for women of childbearing
potential: negative urine or serum pregnancy test within 28 days of study treatment
and confirmed prior to treatment on day 1. Postmenopausal is defined as: amenorrheic
for 1 year or more following cessation of exogenous hormonal treatments, luteinizing
hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal range
for women under 50, radiation-induced oophorectomy with last menses > 1 year ago,
chemotherapy-induced menopause with > 1 year interval since last menses, or surgical
sterilization (bilateral oophorectomy or hysterectomy). Women of childbearing
potential (WoCBP) must utilize acceptable contraception for two weeks before the first
dose of olaparib, for the duration of the study, and for at least 6 months after the
last dose of olaparib
- Hemoglobin >= 10.0 g/dL (with no blood transfusion in the past 28 days) (measured
within 28 days prior to administration of study treatment)
- Absolute neutrophil count (ANC) >= 1.5 x 109/L (> 1500 per mm3) (measured within 28
days prior to administration of study treatment)
- Platelet count >= 100 x 109/L (> 100,000 per mm3) (measured within 28 days prior to
administration of study treatment)
- Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN) (measured within 28
days prior to administration of study treatment)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x ULN unless liver metastases are present, in which case it must be =< 5 x ULN
(measured within 28 days prior to administration of study treatment)
- Serum creatinine clearance (CrCL) >= 51 mL/min by the Cockcroft-Gault formula or by
24-hour urine collection for determination of CrCL (measured within 28 days prior to
administration of study treatment)
Exclusion Criteria:
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site)
- Previous enrollment in the present study
- Prior treatment for ovarian, fallopian tube, or primary peritoneal cancer
- Histology showing mucinous or low grade epithelial carcinoma
- Participation in another clinical study with an investigational product (IP) during
the last 4 weeks
- History of another primary malignancy except for: malignancy treated with curative
intent and with no known active disease >= 5 years before the first dose of study drug
and of low potential risk for recurrence, adequately treated non-melanoma skin cancer
or lentigo maligna without evidence of disease, and/or adequately treated carcinoma in
situ without evidence of disease e.g., cervical cancer in situ
- Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible
cardiac conditions, as judged by the investigator (e.g., unstable ischemia,
uncontrolled symptomatic arrhythmia, congestive heart failure, mean QT interval
corrected for heart rate with Fridericia's correction (QTcF) prolongation > 500 ms,
electrolyte disturbances, etc.), or patients with congenital long QT syndrome
- Any unresolved toxicity (> CTCAE grade 2) from previous anti-cancer therapy, excluding
alopecia
- History of hypersensitivity to olaparib or its excipients
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diatheses including any subject known to have evidence of acute or chronic
hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or otherwise
immunocompromised subjects, or psychiatric illness/social situations that would limit
compliance with study requirements or compromise the ability of the subject to give
written informed consent
- History of leptomeningeal carcinomatosis
- Subjects who are pregnant and/or breast-feeding
- Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of subject safety or study results
- Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive
of but not limited to surgery, radiation and/or corticosteroids. The subject 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
- Subjects with uncontrolled seizures
- Patients with myelodysplastic syndrome/acute myeloid leukemia or with features
suggestive of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML)
- Patients unable to swallow orally administered medication and patients with
gastrointestinal disorders likely to interfere with absorption of the study medication
- Any previous treatment with PARP inhibitor, including olaparib
- 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, 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 allogeneic bone marrow transplant or double umbilical cord blood
transplantation (dUCBT)
- Whole blood transfusions in the last 120 days prior to entry to the study (packed red
blood cells and platelet transfusions are acceptable outside of 28 days prior to
treatment)
- Non-English speakers will be excluded from participating in the patient-reported
outcomes component of the study
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