Testing the Combination of the Study Drugs Cediranib and Olaparib in Recurrent Ovarian Cancer

Inclusion Criteria:

Participants must have histologically or cytologically confirmed ovarian cancer, peritoneal cancer or fallopian tube cancer and must have a histological diagnosis of either high grade serous or high grade endometrioid cancer based on local histopathological findings; participants with a deleterious BRCA-mutation on a commercial Clinical Laboratory Improvement Amendments (CLIA) assay with other high-grade histologies are also eligible

Due to the long acceptance of BRCA testing through Myriad, Myriad testing will be accepted as documentation of a deleterious mutation; if testing for BRCA is done by other organizations, documentation from a qualified medical professional (e.g., ovarian cancer specialty physician involved in the field, high risk genetics physician, genetics counselor) listing the mutation and confirming that the laboratory results show a recognized germline deleterious BRCA1 or BRCA2 mutation or BRCA rearrangements is required to document the presence of a deleterious mutation
Participants must have measurable disease via Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan, MRI, or calipers by clinical exam
Patients may not have received prior poly ADP ribose polymerase (PARP) inhibitors
Patients may have received but may not have progressed on prior anti-angiogenic therapy in the upfront setting

For platinum sensitive cohort

Cancer that has not progressed within 6 months of the last receipt of platinum-based chemotherapy
No limit on the number of platinum-based lines
No more than one prior non-platinum based line of therapy in the recurrent setting

For platinum-resistant or -refractory cohort

Disease that has progressed within 6 months of the last receipt of platinum-based chemotherapy
No more than 1 prior line of therapy in the platinum-resistant/-refractory setting
No limit on number of prior lines received in the platinum-sensitive setting prior to development of platinum-resistance (defined as disease progression within 6 months of platinum-based chemotherapy)
Hormonal therapies used as single agents (i.e. tamoxifen, aromatase inhibitors) will not count towards line limit considerations
Age >= 18 years of age. Because no dosing or adverse event data are currently available on the use of cediranib or olaparib in patients under the age of 18, children are excluded from this study
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Leukocytes >= 3,000/mcL
Absolute neutrophil count >= 1,500/mcL
Hemoglobin >= 10 g/dL
Platelets >= 100,000/mcL
Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
Creatinine less than or equal to the institutional upper limit of normal or creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
Proteinuria less than or equal to 1+ proteinuria on two consecutive dipsticks taken no less than week apart, or a urine protein:creatinine (UPC) ratio of =< 1
Coagulation parameters (international normalized ratio [INR], activated partial thromboplastin time [aPTT]) =< 1.25 x ULN institutional limits, except where a lupus anti-coagulant has been confirmed
Presence of biopsiable disease and willingness to undergo pre-treatment and on-treatment biopsy
The effects of olaparib and cediranib on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and up to 3 months after end of treatment; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction and thyroid stimulating hormone (TSH) less than or equal to the upper limit of normal
Patients must be able to tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of cediranib or olaparib
Ability to understand and the willingness to sign a written informed consent document
Willingness to release and confirmed availability of archival tissue sample for research purposes
Willingness and ability to check and record daily blood pressure readings; blood pressure cuffs will be provided to patients

Exclusion Criteria:

Participants may not have had chemotherapy or radiation therapy (RT) within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study and must have recovered to =< grade 1 from adverse events due to agents administered more than 3 weeks earlier; patients should not have received hormonal therapy for treatment of their cancer within 2 weeks of study entry
Participants should not have received any other investigational agents nor have participated in an investigational trial within the past 4 weeks
Participants may not have had prior use of PARP inhibitors; patients may not have received prior treatment affecting the VEGF pathway in the recurrent setting, including but not limited to thalidomide, bevacizumab, sunitinib, or sorafenib
Participants may not have any evidence of ongoing inadequately controlled hypertension (defined as a systolic blood pressure [BP] of > 140 mmHg or a diastolic BP of > 90 mmHg); patients with hypertension may not be on more than three antihypertensive medications for management of their blood pressure (medications that combine two anti-hypertensives into one are considered as two medications); it is strongly recommended that patients who require three antihypertensive medications for baseline management of pre-existing hypertension be actively followed by a cardiologist or blood pressure specialist for management of BP while on protocol
Participants may not have had any prior history of hypertensive crisis or hypertensive encephalopathy
Participants may not have had history of abdominal fistula or gastrointestinal perforation; patients with a history of abdominal fistula will be considered eligible if the fistula has healed or was surgically repaired, there has been no evidence of fistula for at least 6 months, and patient is deemed to be at low risk of recurrent fistula
Participants may not have had a history of intra-abdominal abscess within the past 3 months
Participants may not have current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel obstruction within 3 months prior to starting study drugs
Participants may not have a dependency on intravenous (IV) hydration or total parenteral nutrition (TPN)

Participants with any concomitant or prior invasive malignancies are ineligible with the following exceptions:

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 greater than IA, grade 1 or 2, no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell, or other International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions
Prior cancer treated with curative intent with no evidence of recurrent disease 3 years following diagnosis and judged by the investigator to be at low risk of recurrence

Participants with any of the following:

History of myocardial infarction within six months
Unstable angina
New York Heart Association (NYHA) classification of III or IV
If cardiac function assessment is clinically indicated or performed: participants will be ineligible if left ventricular ejection fraction (LVEF) is less than normal per institutional guidelines, or < 55%, if the threshold for normal is not otherwise specified by institutional guidelines

Patients with any of the following risk factors should have a baseline cardiac function 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 with history of myocardial infarction within 6 months are excluded from the study
A NYHA classification of II controlled with treatment
Prior history of impaired cardiac function
Participants may not have had a history of a stroke or transient ischemic attack within six months
Participants should not have clinically significant peripheral vascular disease or vascular disease (including aortic aneurysm or aortic dissection)
Participants may not have a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting cediranib
Participants should not have any uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans are ineligible; screening imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated; patients with treated brain metastases must demonstrate stable post-therapeutic imaging and resolution of any associated symptoms and must be stably off steroids with no symptoms for at least 6 months following therapy prior to starting study drug
Participants may not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib or olaparib
Participants receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) or moderate inhibitors of CYP3A4 are ineligible; the study team should check a frequently-updated medical reference for a list of drugs to avoid or minimize use of; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product; dihydropyridine calcium-channel blockers are permitted for management of hypertension
Pregnant women are excluded from this study because olaparib and cediranib have the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib and cediranib, breastfeeding should be discontinued if the mother is treated with cediranib and olaparib; these potential risks may also apply to other agents used in this study
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cediranib or olaparib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
Participants should not have evidence of coagulopathy or bleeding diathesis; therapeutic anticoagulation for prior thromboembolic events is permitted

Current use of a prohibited medication; the following medications or non-drug therapies are prohibited:

Other anti-cancer therapy while on study treatment
Prophylactic use of bisphosphonates in patients without bone disease, except for the treatment of osteoporosis
Because the composition, PK, and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, cannabis, St. John's wort, kava, ephedra [ma huang], ginkgo biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng)
Raloxifene is allowed for patients taking it for bone health
Participants may not have any features suggestive of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated