Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase I/II Study of Cediranib and Olaparib in Combination for Treatment of Recurrent Papillary-Serous Ovarian, Fallopian Tube, or Peritoneal Cancer or for Treatment of Recurrent Triple-Negative Breast Cancer
Brief Summary: This partially randomized phase I/II trial studies the side effects and the best dose of cediranib maleate and olaparib and to see how well they work compared to olaparib alone in treating patients with ovarian, fallopian tube, peritoneal, or triple-negative breast cancer that has returned after a period of improvement (recurrent). Cediranib maleate may help keep cancer cells from growing by affecting their blood supply. Olaparib may stop cancer cells from growing abnormally. The combination of cediranib maleate and olaparib may be safe, tolerable and/or effective in treating patients with recurrent ovarian, fallopian tube, or peritoneal cancer or recurrent triple-negative breast cancer.


Options:
A: Inclusion Criteria:

* Capable of providing signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the Clinical Study Protocol (CSP).
* Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
* Female ≥18 years of age at the time of signing the ICF.
* Eastern Cooperative Oncology Group performance status 0 to 1 within 28 days of randomization.
* Participants with relapsed histologically confirmed diagnosis of high grade epithelial ovarian cancer (including primary peritoneal and/or fallopian tube cancer), with disease relapse on or after completion of PARPi maintenance therapy and who have not received any intervening systemic treatment since discontinuation of PARPi (this excludes the platinum based chemotherapy received during Screening Part 1 of this study).
* A minimum of 6 months of prior PARPi treatment received in the maintenance setting for PSR ovarian cancer (a minimum of 12 months is required if the participant received PARPi maintenance following first line chemotherapy). If the prior PARPi used was olaparib then participants must have received treatment without significant toxicity or the need for a permanent dose reduction.
* Disease relapse in the second line (first relapse) or third line (second relapse) setting.
* Able to provide and consent to the collection of a contemporaneous tumor tissue biopsy and blood sample.
* Able to provide a Formalin Fixed Paraffin Embedded archival tumour tissue block from the time of primary tumour diagnosis (taken ideally prior to receiving any systemic treatment, and definitely prior to first PARPi treatment) for prospective Breast cancer susceptibility gene (BRCA) status testing. If tumour blocks are unavailable, tissue sections are acceptable with a minimum requirement of at least 20 unstained sections on uncharged slides without cover slips. Fine needle aspirates are not acceptable.
* Where the patient has previously been tested for germline or somatic BRCA alterations using a verified and well-validated test in line with local regulations, performed in a locally accredited laboratory (eg, College of American Pathologists/Clinical Laboratory Improvement Amendments laboratory, where available), and signed consent to provide a copy of the BRCA report.
* Platinum-sensitive disease at the time of disease relapse, i.e, platinum-treatment free survival of greater than 6 months as defined by the Gynecological Cancer Intergroup (Wilson et al 2017).
* For the platinum-based chemotherapy course received following pre screening (Part 1) and prior to entering the main screening (Part 2).
* Any prior palliative radiation must have been completed at least 7 days prior to the start of study drugs, and participants must have recovered from any acute adverse effects prior to the start of study treatment.
* Normal organ and bone marrow function measured within 28 days prior to randomization.
* Participant is willing and able to comply with the CSP for the duration of the study including undergoing treatment and scheduled visits and examinations.
* Participants must have a life expectancy of ≥16 weeks.
* Participants must be able to swallow tablets whole.
* For inclusion in the optional (deoxyribonucleic acid) genetics research, study participants must fulfil the following criterion:

Provide informed consent for the genetic sampling and analyses. If a participant declines to participate in the genetics research, there will be no penalty or loss of benefit to the participant. A participant who declines genetics research participation will not be excluded from any other aspect of the main study.

* Participant's body weight must be \>30 kg.
* Postmenopausal or evidence of non-childbearing status for women of childbearing potential.
* Women of childbearing potential and their partners, who are sexually active, must agree to the use of 2 highly effective forms of contraception in combination from the signing of the informed consent (Screening Part 1), throughout the period of taking study treatment and for at least 6 months after the last dose of study drug(s).

Exclusion Criteria:

* Participants who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen or during the period between completion of chemotherapy and first dose of study treatment.
* Participants with current signs or symptoms of bowel obstruction, including sub-occlusive disease, related to underlying disease.
* History of leptomeningeal carcinomatosis.
* Participants with symptomatic uncontrolled brain metastases.

  1. A scan to confirm the absence of brain metastases is not required.
  2. Participants whose brain metastases have been treated may participate provided they show radiographic stability. In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade \<2) either, without the use of steroids, or are stable on a steroid dose of ≤10 mg/day of prednisone or its equivalent and stable on anti convulsants if required for at least 14 days prior to the start of treatment.
  3. Participants with spinal cord compression are not eligible unless considered to have received definitive treatment for this and have evidence of clinically SD for \>28 days and have not received steroid treatment for at least 14 days prior to the start of study treatment.
* History of another primary malignancy except for:

  1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence;
  2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
  3. Adequately treated carcinoma in situ without evidence of disease.
* Major surgical procedures (as defined by the investigator) ≤28 days of beginning study treatment, or minor surgical procedures ≤7 days. No waiting period required following port a cath or other central venous access placement.
* Persistent toxicities (≥CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia and CTCAE Grade 2 peripheral neuropathy. Note: participants with signs of ongoing complications from radiation therapy are not eligible for this study.
* Participants with myelodysplastic syndrome (MDS) /acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
* Resting electrocardiogram indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator, or participants with congenital long QT syndrome.
* Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
* History of allogeneic organ transplantation including previous allogeneic bone marrow transplant or double umbilical cord blood transplantation.
* History of active primary immunodeficiency.
* Active infection including tuberculosis (TB), hepatitis B (known positive hepatitis B virus \[HBV\] surface antigen \[HBsAg\] result), hepatitis C (HCV), or human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies). Participants with a past or resolved HBV infection are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid.
* Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations.
* Current dependency on total parenteral nutrition or intravenous (iv) fluid hydration.
* Whole blood transfusions in the last 120 days prior to entry to the study.
* Cytotoxic chemotherapy, hormonal or non hormonal targeted therapy within 21 days of Cycle 1, Day 1 is not permitted. The participant can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 5 days prior to study treatment.
* Participation in another clinical study with an IP during the chemotherapy course immediately prior to randomisation or during the course of the study.
* Previous treatment with ceralasertib or other ataxia telangiectasia and Rad3-related protein, Checkpoint kinase 1 or deoxyribonucleic acid damage response inhibitor (excluding PARPi).
* Exposure to a small molecule IP within 30 days or 5 half-lives (whichever is longer) prior to randomization. The minimum washout period for immunotherapy and bevacizumab shall be 42 days.
* Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment.
* Concomitant use of known strong cytochrome P450 (CYP) 3A inhibitors or moderate CYP3A inhibitors. The required washout period prior to starting study treatment is 2 weeks.
* Concomitant use of known strong CYP3A inducers or moderate CYP3A inducers. The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
* Involvement in the planning and/or conduct of the study (applies to Sponsor staff and/or staff at the study site).
* Previous randomization in the present study.
* Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
* Pregnant or lactating women.
B: Inclusion Criteria:

* Newly diagnosed advanced (FIGO stage III-IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer.
* Completed cytoreductive surgery, including at least a bilateral salpingo-oophorectomy and partial omentectomy, either prior to chemotherapy (primary surgery) or following neoadjuvant chemotherapy (interval debulking)
* Completed first-line platinum-based chemotherapy and surgery with a response, in the opinion of the Investigator
* Sufficient tumor tissue for planned analysis
* ECOG performance status of 0 or 1
* Patients must be 20 years of age to consent in Japan, Taiwan and South Korea; in all other participating countries patients must be 18 years of age to consent

Exclusion Criteria:

* Pure sarcomas or borderline tumors or mucinous tumors
* Active second malignancy
* Known central nervous system brain metastases
* Any prior treatment for ovarian cancer, other than the first-line platinum regimen
* Evidence of interstitial lung disease or active pneumonitis
* Active, known or suspected autoimmune disease
* Condition requiring active systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications
C: Inclusion Criteria:

* Female patients with histologically diagnosed serous ovarian cancer or recurrent serous ovarian cancer.
* Patients must have completed at least 2 previous courses of platinum containing therapy; the patient must have been platinum sensitive to the penultimate chemo regimen.
* For the last chemotherapy course prior to enrolment on the study, patients must have demonstrated an objective stable maintained response (partial or complete response) and this response needs to be maintained until completion of chemotherapy.
* Patients must be treated on the study within 8 wks of completion of their final dose of the platinum containing regimen.

Exclusion Criteria:

* Previous treatment with PARP inhibitors including AZD2281
* Patients with low grade ovarian carcinoma.
* Patients who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen prior to enrolment on the study
* Patients receiving any chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study entry (or a longer period depending on the defined characteristics of the agents used).
D: Inclusion Criteria:

* PHASE I: Participants must have histologically or cytologically confirmed epithelial ovarian cancer, primary peritoneal serous cancer, fallopian tube cancer, or triple-negative breast cancer
* PHASE II: Participants must have histologically or cytologically grade 2 or 3 (high-grade) papillary-serous or endometrioid epithelial ovarian cancer, primary peritoneal serous cancer, or fallopian tube cancer; participants with epithelial ovarian, primary peritoneal, or fallopian tube cancers of other high-grade histologies who carry a known deleterious breast cancer gene (BRCA) germline mutation by standard clinical testing (Myriad BRAC Analysis) will also be considered eligible
* PHASE I-T: Participants must have histologically or cytologically confirmed epithelial ovarian cancer, primary peritoneal serous cancer, or fallopian tube cancer
* Ovarian cancer, primary peritoneal, and fallopian tube participants in the Phase 1 and Phase 1-T portions of this trial must have either measurable cancer by RECIST 1.1 criteria or an elevated cancer antigen (CA)125 level at least twice the upper limit of normal on two separate occasions at least 1 day but not more than 3 months apart; at least one of the samples should be within 1 week of starting treatment; patients with both an elevated CA125 and measurable cancer will be followed by RECIST 1.1 criteria; patients with only an elevated CA125 level will be followed by modified Gynecologic Cancer Intergroup (GCIG) criteria
* Participants in the Phase II portion of the trial must have measurable disease by RECIST 1.1 criteria
* Breast cancer participants must have measurable disease by RECIST criteria
* PRIOR THERAPY PHASE I and PHASE I-T:

  * Prior chemotherapy for ovarian cancer patients must have included a first-line platinum-based regimen with or without intravenous consolidation chemotherapy
  * Breast cancer patients must have recurred post both an Adriamycin- and taxane-containing regimen
  * Prior hormonal-based therapy for ovarian, primary peritoneal serous, fallopian tube cancer, or breast cancer is acceptable
  * Patients may not have had a prior PAR polymerase (PARP)-inhibitor in the recurrent or metastatic setting; prior treatment with BSI-201 (iniparib) is allowed
  * Patients may not have had a prior anti-angiogenic agent in the recurrent or metastatic setting
* PRIOR THERAPY PHASE II:

  * Prior chemotherapy must have included a first-line platinum-based regimen with or without intravenous consolidation chemotherapy
  * Prior hormonal-based therapy for ovarian, primary peritoneal serous, or fallopian tube cancer is acceptable
  * Patients may not have previously received a PARP-inhibitor; prior treatment with BSI-201 is allowed
  * Patients may not have had a prior anti-angiogenic agent in the recurrent setting
  * Patients may have received up to 1 non-platinum-based line of therapy in the recurrent setting
  * Patients may have received an unlimited number of platinum-based therapies in the recurrent setting
  * Patients should have platinum-sensitive disease, where platinum-sensitive disease is defined as having had a \> 6 month interval since last receiving platinum therapy prior to disease recurrence; patients must have had a prior response while on the platinum-containing regimen and cannot have experienced disease progression while receiving platinum
* Subjects may begin cediranib and olaparib at least 3 weeks after their last dose of chemotherapy or hormonal therapy, assuming they are otherwise eligible
* Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of cediranib or olaparib in participants \< 18 years of age, children are excluded from this study but will be eligible for future pediatric trials
* Estimated life expectancy of greater than 6 months
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky \> 60%)
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Hemoglobin \> 9 g/dL

  * For patients enrolled to the Phase 1-T portion of the protocol, the hemoglobin should be \>= 10 g/dL
* Total bilirubin within 1.5 times the upper limit of normal institutional limits
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
* Creatinine =\< the institutional upper limit of normal or creatinine clearance \>= 60 mL/min/1.73 m\^2 for subjects with creatinine levels above institutional normal
* Less than or equal to 1+ proteinuria on two consecutive dipsticks taken no less than 1 week apart, or \< 1 gm protein on 24-hour urine collection or a urine protein: creatinine ratio of \< 1
* Troponin T or I within normal institutional limits
* Coagulation parameters (international normalized ratio \[INR\], activated partial thromboplastin time \[aPTT\]) within 1.25 x upper limit of normal institutional limits, except where a Lupus anti-coagulant has been confirmed
* Toxicities of prior therapy (except alopecia) should be resolved to less than or equal to grade 1 as per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0); patients with long-standing stable grade 2 neuropathy may be considered after discussion with the overall principal investigator (PI)
* Subjects with treated limited stage basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the breast or cervix are eligible; subjects with prior cancer treated with a curative intent with no evidence of recurrent disease 5 years following diagnosis and judged by the investigator to be at low risk of recurrence are eligible; subjects with any other concomitant or prior invasive malignancies are ineligible
* Patients who have the following risk factors are considered to be at increased risk for cardiac toxicities; these patients should have increased monitoring:

  * Prior treatment with anthracyclines
  * Prior treatment with trastuzumab
  * A New York Heart Association classification of II controlled with treatment
  * Prior central thoracic radiation therapy (RT), including RT to the heart
  * History of myocardial infarction within 12 months (patients with history of myocardial infarction within 6 months are excluded from the study)
* The effects of cediranib and olaparib 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 for 3 months following treatment discontinuation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
* Ability to understand and the willingness to sign a written informed consent
* Patients must be able to tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of cediranib or olaparib
* Patients must be willing and able to check and record daily blood pressure readings

Exclusion Criteria:

* Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier
* Participants may not be receiving any other investigational agents nor have participated in an investigational trial within the past 4 weeks; subjects may not have received prior treatment affecting the vascular endothelial growth factor (VEGF) pathway in the recurrent setting, including thalidomide, bevacizumab, sunitinib, or sorafenib; in the Phase I portion of the trial, subjects may not have received prior treatment with oregovomab (OvaRex) or any other antibodies that may interfere with CA-125 measurements
* Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or MRI scans should not be included on this study, since neurologic dysfunction may confound the evaluation of neurologic and other adverse events; 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 and resolution of any associated symptoms must demonstrate stable post-therapeutic imaging for at least 6 months following therapy prior to starting study drug
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib maleate or olaparib
* Participants receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible; dihydropyridine calcium-channel blockers are permitted for management of hypertension
* Patients with any of the following:

  * History of myocardial infarction within six months
  * Patients with corrected QT (QTc) prolongation \> 500 msec or other significant electrocardiogram (ECG) abnormality noted within 14 days of treatment

    * For patients enrolled in the Phase 1-T portion of the protocol, the QTc should not exceed 470 msec
  * New York Heart Association (NYHA) classification of III or IV
  * If cardiac function assessment is clinically indicated or performed: left ventricular ejection fraction (LVEF) less than normal per institutional guidelines, or \< 55%, if threshold for normal not otherwise specified by institutional guidelines
  * Condition requiring concurrent use of drugs or biologics with pro-arrhythmic potential
* History of stroke or transient ischemic attack within six months
* Patients may not have any evidence of pre-existing inadequately controlled hypertension (defined as a systolic blood pressure \[BP\] of \> 140 mmHg or a diastolic BP of \> 90 mmHg), and must have a normal blood pressure (=\< 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 up to a maximum of three antihypertensive medications; patients who are on three antihypertensive medications must be actively followed by a cardiologist or blood pressure specialist for management of blood pressure while on protocol
* Any prior history of hypertensive crisis or hypertensive encephalopathy
* Clinical significant peripheral vascular disease or vascular disease (aortic aneurysm or aortic dissection)
* Unstable angina
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting cediranib
* History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
* Current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel obstruction within 3 months prior to starting study drugs
* Current dependency on intravenous (IV) hydration or total parenteral nutrition (TPN)
* Evidence of coagulopathy or bleeding diathesis; therapeutic anticoagulation for prior thromboembolic events is permitted
* 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
* Pregnant women are excluded from this study because cediranib and olaparib are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with cediranib and olaparib, breastfeeding should be discontinued if the mother is treated with cediranib or olaparib; these potential risks may also apply to other agents used in this study
* Known human immunodeficiency virus (HIV)-positive individuals are ineligible because of the potential for pharmacokinetic interactions with cediranib or olaparib; in addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy
* Patients may not use natural herbal products or other "folk remedies" while participating in this study
* No features suggestive of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated

Answer: D