Testing the Combination of the Study Drugs Cediranib and Olaparib in Recurrent Ovarian Cancer
Condition: Fallopian Tube Carcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Endometrioid Adenocarcinoma; Ovarian Carcinoma; Ovarian High Grade Serous Adenocarcinoma; Primary Peritoneal Carcinoma; Primary Peritoneal Endometrioid Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma
MeSH terms: Carcinoma; Adenocarcinoma; Cystadenocarcinoma, Serous; Carcinoma, Endometrioid
Intervention: Biopsy; Biospecimen Collection; Cediranib Maleate; Computed Tomography; Echocardiography; Magnetic Resonance Imaging; Multigated Acquisition Scan; Olaparib; Questionnaire Administration
Intervention description: Undergo biopsy of tumor; Undergo blood sample collection; Given PO; Undergo CT scan; Undergo echocardiogram; Undergo MRI scan; Undergo MUGA; Given PO; Ancillary studies
Intervention MeSH terms: Olaparib; Poly(ADP-ribose) Polymerase Inhibitors; Cediranib; Maleic acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 70.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well olaparib and cediranib maleate work in treating patients
      with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period
      of improvement (recurrent). Olaparib and cediranib maleate may stop the growth of tumor cells
      by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        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