Testing the Use of A Single Drug (Olaparib) or the Combination of Two Drugs (Cediranib and Olaparib) Compared to the Usual Chemotherapy for Women With Platinum Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Inclusion Criteria:

• Patients must have platinum-sensitive recurrent high-grade serous or high-gradeendometrioid ovarian, primary peritoneal, or fallopian tube cancers; patients withother (clear cell, mixed epithelial, undifferentiated carcinoma, or transitionalcell carcinoma) high-risk histologies are also eligible, provided that the patienthas a known deleterious germline BRCA1 or BRCA2 mutation identified through testingat a clinical laboratory; Note: Due to the long acceptance of germline BRCA testingthrough Myriad, Myriad testing will be accepted; if testing for germline BRCA isdone by other organizations, documentation from a qualified medical professional (e.g., ovarian cancer specialty physician involved in the field, high risk geneticsphysician, genetics counselor) listing the mutation and confirming that thelaboratory results showed a recognized germline deleterious BRCA1 or BRCA2 mutationor BRCA rearrangement is required; please collect a copy of Myriad or other BRCAmutational analysis (positive or VUS or negative) reports

• Platinum-sensitive disease defined as no clinical or radiographic evidence ofdisease recurrence for > 6 months (or 182 days) after last receipt ofplatinum-based therapy

• Patients must have had a complete clinical response to their prior line ofplatinum therapy and cannot have had progression through prior platinum-basedtherapy

• Patients must have signed an approved informed consent and authorization permittingrelease of personal health information

• Patients must have evaluable disease - defined as one of the following:

• Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurable disease OR

• Evaluable disease (defined as solid and/or cystic abnormalities on radiographicimaging that do not meet RECIST 1.1 definitions for target lesions OR ascitesand/or pleural effusion that has been pathologically demonstrated to bedisease-related) AND a cancer antigen 125 (CA125) that has doubled from thepost-treatment nadir and is also greater than 2 times upper limit of normal (ULN)

• Prior therapy:

• Prior chemotherapy must have included a first-line platinum-based regimen withor without intravenous consolidation chemotherapy

• Patients may have received an unlimited number of platinum-based therapies inthe recurrent setting

• Patients may have received up to 1 non-platinum-based line of therapy in therecurrent setting; prior hormonal therapy will not be considered to count asthis non-platinum-based line

• Patients may not have had a prior anti-angiogenic agent in the recurrentsetting; prior use of bevacizumab in the upfront or upfront maintenance settingis allowed

• Patients may not have previously received a poly adenosine diphosphate (ADP)ribose polymerase (PARP)-inhibitor

• Prior hormonal-based therapy for ovarian, primary peritoneal, or fallopian tubecancer is acceptable

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance statusof 0, 1 or 2 (Karnofsky >= 60%)

• Absolute neutrophil count >= 1,500/mcL

• Platelets >= 100,000/mcL

• Hemoglobin >= 10 g/dL

• Creatinine =< the institutional upper limit of normal (ULN) OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

• Urine protein: creatinine ratio (UPC) of =< 1 or less than or equal to 2+proteinuria on two consecutive dipsticks taken no less than 1 week apart; UPC is thepreferred test; patients with >= 2+ proteinuria on dipstick must also have a 24 hoururine collection demonstrating =< 500 mg over 24 hours

• Total bilirubin =< 1.5 x the institutional ULN

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 times institutional ULN

• Toxicities of prior therapy (excepting alopecia) should be resolved to less than orequal to grade 1 as per National Cancer Institute-Common Terminology Criteria forAdverse Events (NCI-CTCAE); patients with long-standing stable grade 2 neuropathymay be considered after discussion with the overall principal investigator (PI), butmay not receive carboplatin and paclitaxel as the reference regimen, if randomizedto that arm

• Patients must be able to swallow and retain oral medications and withoutgastrointestinal illnesses that would preclude absorption of cediranib or olaparib

• Patients must have adequately controlled blood pressure (BP), with a BP no greaterthan 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility; patients must havea BP of =< 140/90 mmHg taken in the clinic setting by a medical professional within 2 weeks prior to starting study; patients with hypertension may be managed with upto a maximum of three antihypertensive medications; it is strongly recommended thatpatients who are on three antihypertensive medications be followed by a cardiologistor blood pressure specialist for management of blood pressure while on protocol

• Patients must be willing and able to check and record daily blood pressure readings;blood pressure cuffs will be provided to patients randomized to Arm III

• Cediranib has been shown to terminate fetal development in the rat, as expected fora process dependent on VEGF signaling; for this reason, women of child-bearingpotential must have a negative pregnancy test prior to study entry; women ofchild-bearing potential must agree to use two reliable forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, forthe duration of study participation, and for 6 weeks after cediranibdiscontinuation; should a woman become pregnant or suspect she is pregnant whileparticipating in this study, she should inform her treating physician immediately

• Adequately controlled thyroid function, with no symptoms of thyroid dysfunction andthyroid stimulating hormone (TSH) within normal limits

• Age >= 18

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks fornitrosoureas or mitomycin C) of starting treatment or those who have not recoveredfrom adverse events due to agents administered more than 4 weeks earlier; patientsmay not have had hormonal therapy within 2 weeks prior to entering the study;patients receiving raloxifene for bone health as per Food and Drug Administration (FDA) indication may remain on raloxifene absent other drug interactions

• Patients may not be receiving any other investigational agents nor have participatedin an investigational trial within the past 4 weeks

• Patients may not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, pentamidine)

• Patients may not have received prior treatment affecting the vascular endothelialgrowth factor (VEGF) pathway (including, but not limited to thalidomide, sunitinib,pazopanib, sorafenib, and nintedanib); bevacizumab used in the upfront setting inconjunction with chemotherapy and/or as maintenance to treat newly diagnosed diseasewill be allowed

• Patients may not have previously received a PARP inhibitor

• CA-125 only disease without RECIST 1.1 measurable or otherwise evaluable disease

• Patients with untreated brain metastases, spinal cord compression, or evidence ofsymptomatic brain metastases or leptomeningeal disease as noted on CT or MRI scansshould not be included on this study, since neurologic dysfunction may confound theevaluation of neurologic and other adverse events; screening imaging to rule outbrain metastases is not required for screening, but should be performed prior tostudy enrollment if clinically indicated; patients with treated brain metastases andresolution of any associated symptoms must demonstrate stable post-therapeuticimaging for at least 6 months following therapy prior to starting study drug

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to cediranib or olaparib

• Participants receiving any medications or substances that are strong inhibitors orinducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) areineligible; strong inhibitors and inducers of UGT/PgP should be used with caution

• History of gastrointestinal perforation; patients with a history of abdominalfistula will be considered eligible if the fistula was surgically repaired or hashealed, there has been no evidence of fistula for at least 6 months, and patient isdeemed to be at low risk of recurrent fistula

• History of intra-abdominal abscess within the past 3 months

• Current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowelobstruction within 3 months prior to starting study drugs

• Dependency on intravenous (IV) hydration or total parenteral nutrition (TPN)

• Any concomitant or prior invasive malignancies with the following curatively treatedexceptions:

• Treated limited stage basal cell or squamous cell carcinoma of the skin

• Carcinoma in situ of the breast or cervix

• Primary endometrial cancer meeting the following conditions: stage not greaterthan IA, grade 1 or 2, no more than superficial myometrial invasion, withoutvascular or lymphatic invasion; no poorly differentiated subtypes, includingpapillary serous/serous, clear cell, or other International Federation ofGynecology and Obstetrics (FIGO) grade 3 lesions

• Prior cancer treated with a curative intent with no evidence of recurrentdisease 3 years following diagnosis and judged by the investigator to be at lowrisk of recurrence

• Patients with any of the following:

• History of myocardial infarction within six months

• Unstable angina

• Resting electrocardiogram (ECG) with clinically significant abnormal findings

• New York Heart Association (NYHA) classification of III or IV

• If cardiac function assessment is clinically indicated or performed: leftventricular ejection fraction (LVEF) less than normal per institutional guidelines,or < 55%, if threshold for normal not otherwise specified by institutionalguidelines

• Patients with the following risk factors should have a baseline cardiacfunction assessment:

• Prior treatment with anthracyclines

• Prior treatment with trastuzumab

• Prior central thoracic radiation therapy (RT), including RT to the heart

• History of myocardial infarction within 6 to 12 months (patients withhistory of myocardial infarction within 6 months are excluded from thestudy)

• Prior history of impaired cardiac function

• History of stroke or transient ischemic attack within six months

• Any prior history of hypertensive crisis or hypertensive encephalopathy

• Clinically significant peripheral vascular disease or vascular disease (includingaortic aneurysm or aortic dissection)

• Major surgical procedure, open biopsy, or significant traumatic injury within 28days prior to starting cediranib

• Uncontrolled intercurrent illness including, but not limited to ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia (other than atrial fibrillation with controlled ventricular rate), orpsychiatric illness/social situations that would limit compliance with studyrequirements

• Pregnant women are excluded from this study because cediranib and olaparib areagents with the potential for teratogenic or abortifacient effects; because there isan unknown but potential risk of adverse events in nursing infants secondary totreatment of the mother with cediranib and olaparib, breastfeeding should bediscontinued if the mother is treated with cediranib or olaparib; these potentialrisks may also apply to other agents used in this study

• Known HIV-positive individuals are ineligible because of the potential forpharmacokinetic interactions with cediranib or olaparib; in addition, theseindividuals are at increased risk of lethal infections when treated withmarrow-suppressive therapy

• Patients may not use any complementary or alternative medicines including naturalherbal products or folk remedies as they may interfere with the effectiveness of thestudy treatments

• No features suggestive of myelodysplastic syndrome (MDS) or acute myelogenousleukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinicallyindicated

• No prior allogeneic bone marrow transplant or double umbilical cord bloodtransplantation (dUBCT)