Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase I/II, Open-Label, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Oral Rucaparib in Patients With gBRCA Mutation Ovarian Cancer or Other Solid Tumor
Brief Summary: Part 1 (Completed Enrollment) - The purpose of the first part of the study was to evaluate the safety of different doses and dosing regimens of oral rucaparib administered daily to patients with solid tumors.

Part 2A (Completed Enrollment) and Part 2B (Completed Enrollment) - The purpose of the second part of the study is to determine the safety and clinical activity of the RP2D of oral rucaparib administered daily to patients with a known deleterious BRCA mutation (germline or somatic).

Part 3 (Completed Enrollment) - The purpose of the third part of the study is to further evaluate PK of higher dose strength tablets at the RP2D in patients with any advanced solid tumor, inclusive of lymphoma, with evidence of a BRCA mutation (germline or somatic).


Options:
A: 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
B: DISEASE CHARACTERISTICS:

* Postmenopausal, as defined by meeting 1 of the following criteria:

  * More than 12 months of amenorrhea after natural menopause or hysterectomy
  * Received more than 12 months of hormone replacement therapy for menopausal symptoms
* No prior ovarian malignancy
* No prior bilateral oophorectomy
* Not at high risk for ovarian cancer due to familial predisposition as defined by the UKCCCR Familial Ovarian Cancer Screening Study

PATIENT CHARACTERISTICS:

Age

* 50 to 74

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Not specified

Other

* No active non-ovarian malignancy

  * Prior malignancy allowed provided there is no documented persistent or recurrent disease and patient has not received treatment for more than 1 year

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* Not specified

Endocrine therapy

* See Disease Characteristics

Radiotherapy

* Not specified

Surgery

* See Disease Characteristics

Other

* No concurrent participation in any other ovarian cancer screening study
C: The following eligibility criteria below pertain to patients enrolling into Part 2B of the study.

Inclusion Criteria:

* Have a known deleterious BRCA mutation (gBRCA or sBRCA) (as determined by a local laboratory that has received an international or country-specific, quality standards certification)
* Have evidence of measurable disease as defined by RECIST Version 1.1
* Have sufficient archival FFPE tumor tissue available for planned analyses. Archival tissue from the most recently collected biopsy or debulking surgery should be provided, if available.
* Have a histologically confirmed diagnosis of high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer
* Have received at least three prior chemotherapy regimens and have relapsed disease confirmed by radiologic assessment

Exclusion Criteria:

* Active second malignancy, i.e., patient known to have potentially fatal cancer present for which she may be (but not necessarily) currently receiving treatment

  a. Patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy was completed \>6 months prior and/or bone marrow transplant (BMT) \>2 years prior to first dose of rucaparib
* Prior treatment with any PARP inhibitor.
* Untreated or symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS metastases are eligible provided they have been clinically stable for at least 4 weeks.
* Received treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs 14 days prior to first dose of rucaparib and/or ongoing adverse effects from such treatment \> NCI CTCAE Grade 1 (Grade 2 non-hematologic toxicity to most recent treatment may be permitted with prior advanced approval from Sponsor).
* Hospitalization for bowel obstruction within 3 months prior to enrollment.
D: Inclusion Criteria:

* Histologically confirmed high-grade serous or high-grade endometrioid ovarian, primary peritoneal, or fallopian tube cancers.
* Disease progression within 6 months of completing platinum-based chemotherapy
* Who had received ≥ two lines of chemotherapy
* Provision of informed consent prior to any study specific procedures
* Female aged 20 years older at time of study entry
* Body weight \>30kg
* Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below: 1) Haemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days, 2) Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, 3) Platelet count ≥ 100 x 109/L, 4) Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), 5) Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 3 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN, 6) Patients must have creatinine clearance estimated using the Cockcroft-Gault equation of ≥50 mL/min: Estimated creatinine clearance = (140-age \[years\]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72, 7) a where F=0.85 for females and F=1 for males, 8) Urine protein: creatinine ratio (UPC) ≤1 OR ≤2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart. Patients with 2+ proteinuria on dipstick must also have UPC \<0.5 on 2 consecutive samples. 9) Adequately controlled blood pressure (systolic blood pressure (SBP) ≤140 mmHg; diastolic blood pressure (DBP) ≤ 90mmHg) on maximum of 3 antihypertensive medications. Patients must have a blood pressure (BP) of ≤ 140/90 mmHg taken in the clinic setting by a medical professional within 2 weeks prior to starting study. It is strongly recommended that patients who are on three antihypertensive medications be followed by a cardiologist or a primary care physician for management of BP while on study. 10) Adequately controlled thyroid function, with no symptoms of thyroid dysfunction
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Patients must have a life expectancy ≥ 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: 1) Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments, 2) Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50, 3) radiation-induced oophorectomy with last menses \>1 year ago, 4) chemotherapy-induced menopause with \>1 year interval since last menses, 5) surgical sterilisation (bilateral oophorectomy or hysterectomy)
* Patients is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
* Patients must have evaluable disease - define as one of the following: 12.1 RECIST 1.1 measurable disease OR, 12.2 Evaluable disease (defined as solid and cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions OR ascites and/or pleural effusion that has been pathologically demonstrated to be disease-related) in the setting of a CA125 \> 2 times ULN.
* Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer must be available for central testing. If there is not written confirmation of the availability of an archived tumour sample prior to enrolment the patient is not eligible for the study. For inclusion in i) the optional exploratory genetic research and ii) the optional biomarker research, patients must fulfil the following criteria: 1) Provision of informed consent for genetic research, 2) Provision of informed consent for biomarker research
* If a patient declines to participate in the optional exploratory genetic research or the optional biomarker research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study.

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 or randomization in the present study
* Participation in another clinical study with an investigational product during the last 60 months
* Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
* Any previous treatment with poly ADP ribose polymerase(PARP) inhibitor (including olaparib), anti-PD-1, PD-L1, CTLA-4 (including durvalumab and tremelimumab).
* Other malignancy within the last 5 years 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, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥5 years. Patients with a history of localised triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
* Resting ECG with Corrected QT Interval(QTc) \> 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
* Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
* Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) ≤21 days prior to the first dose of study drug If sufficient wash-out time has not occurred due to the schedule or Pharmacokinetics(PK) properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca/MedImmune and the investigator
* Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
* Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
* 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). The required washout period prior to starting olaparib 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). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
* Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria : 1) Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Principal Investigator. 2) Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Principal Investigator.
* Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of Myelodysplastic syndrome/Acute myeloid leukemia(MDS/AML).
* Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient 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.

Answer: C