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Active Clinical Trials

Olaparib, Cediranib Maleate, and Wee1 Inhibitor AZD1775 in Treating Patients With Recurrent, Refractory, or Metastatic Endometrial Cancer

Active NCT:
03660826
Allegheny General Hospital
Allegheny General Hospital

Forbes Hospital
Forbes Hospital

Jefferson Hospital
Jefferson Hospital

West Penn Hospital
West Penn Hospital

Wexford Health + Wellness Pavilion
Wexford Health + Wellness Pavilion

Sponsor: 
National Cancer Institute (NCI)
Contact: 

For more information, please contact Erin Baldauf by telephone at 412-578-4517 or by email at Erin.Baldauf@ahn.org or Hannah Makarevich by telephone at 412-578-4216 or by email at Hannah.Makarevich@AHN.ORG.

A Randomized Phase II Study Comparing Single-Agent Olaparib, Single Agent Cediranib, and the Combination of Cediranib/Olaparib in Women with Recurrent, Persistent or Metastatic Endometrial Cancer (NRG-GY012)

Purpose: 

This randomized phase II trial studies how well olaparib, cediranib maleate, and Wee1 inhibitor AZD1775 work in treating patients with endometrial cancer that has come back, does not respond to treatment, or has spread to other places in the body. Olaparib, cediranib maleate, and Wee1 inhibitor AZD1775 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Ages Eligible for Study:  18 Years and older   (Adult, Older Adult)

Sexes Eligible for Study:  Female

Accepts Healthy Volunteers:  No

Inclusion Criteria:

Patients must have recurrent or persistent endometrial carcinoma, which is refractory to curative therapy or established treatments; histologic confirmation of the original primary tumor is required; patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.); NOTE: clear cell histology is excluded

Patients must have evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; all patients must have measurable disease; measurable disease is defined by RECIST (version 1.1); measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be > 15 mm in short axis when measured by CT or MRI; patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST version 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

Patients must have signed an approved informed consent and authorization permitting release of personal health information

Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen

Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease according to the following definition: cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa; Note: patients on this non-cytotoxic study are allowed to receive one additional cytotoxic chemotherapy regimen for management of recurrent or persistent disease, as defined above; however, patients are encouraged to enroll on second-line non-cytotoxic studies prior to receiving additional cytotoxic therapy

Patients must have NOT received any non-cytotoxic chemotherapy for management of recurrent or persistent disease; prior hormonal therapy is allowed; hormonal therapy for grade 1 endometrial cancers with low volume or indolent disease is encouraged

Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2 (Karnofsky >= 60%) within 7 days prior to registration

Platelet count >= 100 x 10^9/L

Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

Hemoglobin > 9 mg/dL

Serum creatinine =< the institutional upper limit of normal (ULN) OR a creatinine clearance >= 60 mL/min/1.75 m^2 for patients with creatinine levels above institutional normal

Serum bilirubin =< 1.5 X upper limit of normal (ULN)

Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN

Patients must be able to swallow and retain oral medications and without gastrointestinal

Patients must have adequately controlled blood pressure (BP), with a BP no greater than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility; patients must have a BP of =< 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; it is strongly recommended that patients who are on three antihypertensive medications be followed by a cardiologist or blood pressure specialist for management of blood pressure while on protocol

Patients must be willing and able to check and record daily blood pressure reading

The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Adequately controlled thyroid function, with no symptoms of thyroid dysfunction and thyroid-stimulating hormone (TSH) within normal limits

Exclusion Criteria:

Prior enrollment into a clinical trial including cediranib, olaparib, or AZD1775

Prior chemotherapy, endocrine therapy, radiotherapy, or investigational agents within 4 weeks

Current signs/symptoms of bowel obstruction and/or signs/symptoms of bowel obstruction within the preceding 3 months

History of gastrointestinal perforation; patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired or has healed, there has been no evidence of fistula for at least 6 months, and patient is deemed to be at low risk of recurrent fistula

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

Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible; strong inhibitors and inducers of UGT/PgP should be used with caution

Pregnant women are excluded from this study; 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; in addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy

Prior history of stroke or transient ischemic attack within the last 6 months

Prior history of hypertensive crisis or hypertensive encephalopathy

Major surgical procedure, trauma or open biopsy within 28 days of starting Cediranib

Patients may not use any complementary or alternative medicines including natural herbal products or folk remedies as they may interfere with the effectiveness of the study treatments

No prior allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUBCT)

No features suggestive of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated

Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on CT or MRI scans should not be included on this study; 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 prior to starting study drug

Any concomitant or prior invasive malignancies with the following curatively treated exceptions:

Treated limited stage basal cell or squamous cell

Carcinoma in situ of the breast or cervix

Prior cancer treated with a curative intent with no evidence of recurrent disease 3 years following diagnosis and judged by the investigator to be at low risk of recurrence

History of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib, AZD1775 or olaparib