Inclusion Criteria:

- Histological or cytological documentation of metastatic adenocarcinoma of the biliary
tract

- Patients with previously identified genetic aberrations that are associated with
homologous recombinant repair pathway will be eligible [e.g. somatic mutations in ATM,
ATR, CHEK2, BRCA 1/2, RAD51, BRIP1, PALB2, PTEN, FANC, NBN, EMSY, MRE11, ARID1A] or
germline mutations in the above genes. Clinical Laboratory Improvement Act
(CLIA)-certified assays including commercial tests (Foundation Medicine, Caris,
Tempus) will be allowed

- Measurable disease

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. (Form is
available on the Academic and Community Cancer Research United [ACCRU] web site)

- Life expectancy of >= 16 weeks per estimation of investigator

- Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 7 days prior to
registration)

- Platelet count >= 75,000/mm^3 (obtained =< 7 days prior to registration)

- Hemoglobin >= 9.0 g/dL with no blood transfusion in the past 28 days (obtained =< 7
days prior to registration)

- Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 7 days prior to
registration)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5
x ULN for subjects with liver involvement of their cancer) (obtained =< 7 days prior
to registration)

- Serum creatinine =< 1.5 x ULN (obtained =< 7 days prior to registration)

- Institutional normalized ratio (INR)/partial thromboplastin time (PTT) =< 1.5 x ULN
(obtained =< 7 days prior to registration)

- Exception: Patients who are therapeutically treated with anticoagulant agents
(excluding warfarin) will be allowed to participate provided that no prior
evidence of underlying abnormality in coagulation parameters exists. Close
monitoring of at least weekly evaluations will be performed until INR/PTT is
stable based on a measurement that is pre-dose as defined by the local standard
of care

- Alkaline phosphatase limit =< 2.5 x ULN (=< 5 x ULN for patients with liver
involvement of their cancer) (obtained =< 7 days prior to registration)

- Creatinine clearance estimated of >= 51 mL/min using the Cockcroft-Gault equation
(obtained =< 7 days prior to registration)

- Negative serum pregnancy test done =< 28 days prior to registration and confirmed
prior to treatment on day 1, for women of childbearing potential, postmenopausal women
or women of childbearing potential with evidence of non-childbearing status.

- 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 post-menopausal range for women under 50

- Radiation-induced oophorectomy with last menses > 1 year ago

- Chemotherapy-induced menopause with > 1 year interval since last menses

- Surgical sterilization (bilateral oophorectomy or hysterectomy)

- Provide informed written consent

- Willing to return to enrolling institution for follow-up (during the active monitoring
phase of the study)

- Willing to provide blood and tissue for correlative purposes

- Prior exposure or completion of platinum based chemotherapy

Exclusion Criteria:

- Platinum refractory disease (evidence disease progression on platinum based
chemotherapy regimen or =< 6 months of completion of platinum based chemotherapy
regimen)

- Patient has received prior systemic anti-cancer therapy, tumor embolization or
radiotherapy =< 4 weeks prior to registration

- Major surgical procedure, open biopsy, or significant traumatic injury =< 28 days
prior to registration

- NOTE: Patients must have recovered from any effects of any major surgery

- Congestive heart failure - New York Heart Association (NYHA) >= class II

- Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible
cardiac conditions, as judged by the investigator (eg. unstable ischemia, uncontrolled
symptomatic arrhythmia, corrected QT interval by Fridericia's correction formula
[QTcF] prolongation > 500 ms, electrolyte disturbances, etc.), or patients with
congenital long QT syndrome. Cardiac arrhythmias requiring anti-arrhythmic therapy.

- NOTE: Pacemaker, beta blockers or digoxin are permitted

- Uncontrolled hypertension. (Systolic blood pressure > 140 mmHg or diastolic pressure >
90 mmHg despite optimal medical management)

- History of or current pheochromocytoma

- Arterial or venous thrombotic or embolic events such as cerebrovascular accident
(including transient ischemic attacks), deep vein thrombosis or pulmonary embolism =<
6 months prior to registration

- Ongoing infection > grade 2 National Cancer Institute (NCI)-Common Terminology
Criteria for Adverse Events (CTCAE) version (v)5.0

- Known active hepatitis B or C

- Seizure disorder requiring medication

- Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from
definitive therapy, has a negative imaging study =< 4 weeks of registration and is
clinically stable with respect to the tumor at the time of registration. Patients with
spinal cord compression unless considered to have received definitive treatment for
this and evidence of clinically stable disease for 28 days prior to registration

- NOTE: The patient can receive a stable dose of corticosteroids before and during
the study as long as these were started =< 4 weeks prior to registration

- History of organ allograft (including corneal transplant) or allogenic bone marrow
transplant or double umbilical cord blood transplantation (dUCBT)

- Evidence or history of bleeding diathesis or any hemorrhage or bleeding event > CTCAE
v5.0 grade 3, =< 4 weeks prior to registration

- Non-healing wound, ulcer, or bone fracture

- Renal failure requiring hemo-or peritoneal dialysis

- Dehydration CTCAE v5.0 grade >= 1

- Substance abuse, medical, psychological or social conditions that may interfere with
the patient?s participation in the study or evaluation of the study results

- Known hypersensitivity to any of the study drugs, study drug classes, or excipients in
the formulation

- Interstitial lung disease with ongoing signs and symptoms at the time of informed
consent

- Persistent proteinuria of CTCAE v5.0 grade 3 or higher (>= 3.5 g/24 hours [hrs])

- Unable to swallow orally administered medications

- Any malabsorption condition and/or patients with gastrointestinal disorders likely to
interfere with absorption of the study medication

- Unresolved toxicity greater than CTCAE v5.0 grade 2 attributed to any prior
therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity =< grade 2

- Albumin levels < 2.5 g/dl

- Any of the following because this study involves an investigational agent whose
genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
unknown.

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception

- NOTE: Women of childbearing potential and their partners, who are sexually
active, must agree to the use of TWO highly effective forms of contraception in
combination. This should be started from the time of registration and continue
throughout the period of taking study treatment and for at least 1 month after
last dose of study drug(s), or they must totally/truly abstain from any form of
sexual intercourse.

- 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.
Male patients should not donate sperm throughout the period of taking olaparib
and for 3 months following the last dose of olaparib

- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens. 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

- Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
serologically positive and currently receiving antiretroviral therapy.

- NOTE: Patients known to be HIV positive, but without clinical evidence of an
immunocompromised state, are eligible for this trial

- Receiving any other investigational agent which would be considered as a treatment for
the primary neoplasm

- Other malignancy unless curatively treated with no evidence of disease for >= 5 years
prior to registration, except: adequately treated non-melanoma skin cancer, curatively
treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade
1 endometrial carcinoma.

- NOTE: All cancer treatments for cancers that were distinct in a primary site
other than biliary tract cancer must be completed >= 5 years prior to
registration

- Pleural effusion or ascites that causes respiratory compromise (>= CTCAE v5.0 grade 2
dyspnea)

- Previous enrollment in the present study

- Prior exposure to any PARP inhibitor including olaparib

- Known hypersensitivity reaction to olaparib or any of the excipients of the product

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

- 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 (eg.
ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil).

- NOTE: The required washout period prior to registration is 2 weeks

- Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin,
rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John?s Wort) or
moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil).

- NOTE: The required washout period prior to registration is 5 weeks for
enzalutamide or phenobarbital and 3 weeks for other agents

- Patient taking medications or herbal products including grapefruits, grapefruit
hybrids, pomelos, star fruits, Seville oranges, pomegranates, or the juice from any of
these. Note: Patients must discontinue the drug/product >= 7 days prior to
registration

- Patient taking medications with a known risk to prolong the QTc interval and/or cause
Torsades de Pointes. Note: Patients must be discontinued >= 7 days of registration.
Treating physicians may wish to replace the drug(s) that do not carry this risk with
safe alternative(s)

- Concurrent use of warfarin or other warfarin-derived anticoagulant.

- NOTE: Concurrent use of heparin, direct oral anticoagulants, low molecular weight
heparin (LMWH), or fondaparinux is allowed

- 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)

- 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 5/16/23. Questions regarding updates should be directed to the study team contact.