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Protocol Details

A Phase 2 Study of Olaparib and Cediranib for the Treatment of Recurrent Ovarian Cancer

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required


Population Exclusion(s)

Adults who are or may become unable to consent;
Pregnant Women;


Gynecologic Malignancy;
PARP Inhibitor;
VEGFR1-3 Inhibitor;

Recruitment Keyword(s)



Ovarian Cancer;
Peritoneal Cancer;
Fallopian Tube Cancer;
Endometrioid Cancer

Investigational Drug(s)


Investigational Device(s)



Drug: Olaparib
Drug: Cediranib

Supporting Site

National Cancer Institute


Ovarian cancer accounts for about 3 percent of cancers among women. But it causes more deaths than other reproductive cancers. Researchers hope to learn if a combination of drugs can help shrink ovarian cancer tumors by at least 30 percent.


To test any effects of the study drugs cediranib and olaparib. To learn whether biomarkers can help predict who will respond to this study treatment.


Women at least 18 years old with ovarian, fallopian tube, or primary peritoneal cancer that has grown or recurred.


Participants will be screened with a test of how well they do their usual activities. They will have a urine test. They may have heart function tests.

Participants will take one study drug by mouth once a day. They will take the other by mouth twice a day. They will keep a medicines diary.

Participants can stay in the study as long as they tolerate the study drugs. During the study, they will have:

Small pieces of cancer tissue removed. This will be done before starting the study drugs, 4 weeks after that, and maybe at the end of the study.

Blood tests once every 2 weeks during the first 8 weeks of the study, then once a month. They will have 5 other blood draws.

Monthly urine tests.

A weekly office visit or phone call for the first 8 weeks.

Tumor assessment every 8 weeks.

Heart function test every 16 weeks.

Participants will take their blood pressure twice a day and write it in a blood pressure diary.

After finishing treatment, participants will be monitored for 30 days.

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-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 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 requiredto document the presence of a deleterious mutation. Please collect a copy of Myriad or other BRCA mutational analysis (positive or VUS or negative) reports.

-Participants must have measurable disease via 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 greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral CT scan, MRI, or calipers by clinical exam.

-Prior Therapy

--Patients may not have received prior PARP inhibitors

--Patients may have received but may not have progressed on prior antiangiogenic 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 greater than or equal to 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.

-ECOG performance status less than or equal to 2

-Participants must have normal organ and marrow function as defined below:

--Leukocytes greater than or equal to 3,000/mcL

--Absolute neutrophil count greater than or equal to 1,500/mcL

--Hemoglobin greater than or equal to 10 g/dL

--Platelets greater than or equal to 100,000/mcL

--Total bilirubin less than or equal to 1.5 x the institutional upper limit of normal (ULN)

--AST(SGOT)/ALT(SGPT) less than or equal to 3 (SqrRoot) institutional upper limit of normal

--Creatinine less than or equal to the institutional upper limit of normal OR Creatinine clearance greater than or equal to 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 less than or equal to 1.

--Coagulation parameters less than or equal to 1.25 (SqrRoot) ULN institutional limits, except where a (INR, aPTT) 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 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 daily readings. Blood pressure cuffs will be provided to patients.


-Participants may not have had chemotherapy or RT within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study and must have recovered 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 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 IV hydration or 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 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

--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 infarctin 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 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. Patient Drug Information Handout and Wallet Card should be provided to patients.

-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.

-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 on peripheral blood smear or bone marrow biopsy, if clinically indicated.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Jung-Min Lee, M.D.
National Cancer Institute (NCI)
(240) 760-6128

Miroslava Pavelova, C.R.N.P.
National Cancer Institute (NCI)
(240) 858-3241

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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