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Trial record 29 of 4228 for:    Recruiting Studies | NIH

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

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ClinicalTrials.gov Identifier: NCT03660826
Recruitment Status : Recruiting
First Posted : September 7, 2018
Last Update Posted : September 24, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Endometrial Undifferentiated Carcinoma Endometrioid Adenocarcinoma Recurrent Endometrial Serous Adenocarcinoma Recurrent Uterine Corpus Carcinoma Stage IV Uterine Corpus Cancer AJCC v7 Stage IVA Uterine Corpus Cancer AJCC v7 Stage IVB Uterine Corpus Cancer AJCC v7 Drug: Adavosertib Drug: Cediranib Maleate Other: Laboratory Biomarker Analysis Drug: Olaparib Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Four Arm Randomized Phase II Study Comparing Single-Agent Olaparib, Single Agent Cediranib, the Combination of Cediranib/Olaparib and the Combination of Olaparib/Wee1 Inhibitor AZD1775 in Women With Recurrent, Persistent or Metastatic Endometrial Cancer (EEC)
Actual Study Start Date : September 4, 2018
Estimated Primary Completion Date : September 4, 2020
Estimated Study Completion Date : September 4, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Olaparib

Arm Intervention/treatment
Experimental: Arm I (cediranib maleate)
Patients receive cediranib maleate PO QD. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
Drug: Cediranib Maleate
Given PO
Other Names:
  • AZD2171
  • AZD2171 Maleate
  • Recentin

Other: Laboratory Biomarker Analysis
Correlative studies

Experimental: Arm II (olaparib)
Patients receive olaparib PO BID. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Olaparib
Given PO
Other Names:
  • AZD2281
  • KU-0059436
  • Lynparza
  • PARP Inhibitor AZD2281

Experimental: Arm III (cediranib maleate, olaparib)
Patients receive olaparib PO BID and cediranib maleate PO QD. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
Drug: Cediranib Maleate
Given PO
Other Names:
  • AZD2171
  • AZD2171 Maleate
  • Recentin

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Olaparib
Given PO
Other Names:
  • AZD2281
  • KU-0059436
  • Lynparza
  • PARP Inhibitor AZD2281

Experimental: Arm IV (olaparib, Wee1 inhibitor AZD1775)
Patients receive olaparib PO BID and Wee1 inhibitor AZD1775 PO. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.
Drug: Adavosertib
Given PO
Other Names:
  • AZD-1775
  • AZD1775
  • MK-1775
  • MK1775

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Olaparib
Given PO
Other Names:
  • AZD2281
  • KU-0059436
  • Lynparza
  • PARP Inhibitor AZD2281




Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: Time from the date of study enrollment to the investigator-determined date of progression, or death due to any cause, whichever occurs first, assessed up to 5 years ]
    Will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Will be tested using pairwise log-rank tests stratified by the factors.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Time from the date of study enrollment to the date of death regardless of the cause, assessed up to 5 years ]
    Will be tested using pairwise log-rank tests stratified by the factors.

  2. Objective tumor response [ Time Frame: Up to 5 years ]
    Will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Will be tested using pairwise Cochran-Mantel-Haenszel tests stratified by the factors.


Other Outcome Measures:
  1. Incidence of adverse events [ Time Frame: Up to 5 years ]
    Will be assessed by Common Terminology Criteria for Adverse Events version 4.0.

  2. Loss of function of ARID1A [ Time Frame: Up to 5 years ]
    Will be assessed by immunohistochemistry (IHC) and mutational profiles.

  3. Mutations in DNA homologous repair genes [ Time Frame: Up to 5 years ]
    Will be assessed.

  4. Phosphatase and tensin homolog (PTEN) loss [ Time Frame: Up to 5 years ]
    Will be assessed by IHC.

  5. Loss of DNA mismatch repair protein [ Time Frame: Up to 5 years ]
    Will be assessed by IHC. If results are equivocal Microsatellite instability (MSI) may be performed.

  6. TP53 mutation status [ Time Frame: Up to 5 years ]
    Will be assessed by IHC.

  7. P53 expression [ Time Frame: Up to 5 years ]
    Will be assessed by IHC.

  8. Angiogenesis markers [ Time Frame: Up to 5 years ]
    Will be determined by IHC including VEGFA, VEGF R1, VEGFR2 and microvessel density using CD31.

  9. Mutations in WEE1-related genes [ Time Frame: Up to 5 years ]
    Will assess KRAS, MYC, cyclin E, CDKN2A, cyclin D3 in addition to p53 HRD genes.

  10. Surrogate markers for the TCGA molecular subgroups [ Time Frame: Up to 5 years ]
    Will assess p53 IHC, MSI and mutational status of the exonuclease domain of polymerase-epsilon (POLE).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03660826


Locations
United States, Indiana
Saint Vincent Hospital and Health Care Center Recruiting
Indianapolis, Indiana, United States, 46260
Contact: Site Public Contact    317-338-2194    research@stvincent.org   
Principal Investigator: Michael J. Callahan         
United States, Nevada
Women's Cancer Center of Nevada Recruiting
Las Vegas, Nevada, United States, 89169
Contact: Site Public Contact    412-339-5294    Roster@nrgoncology.org   
Principal Investigator: Nicola M. Spirtos         
United States, Ohio
Strecker Cancer Center-Belpre Recruiting
Belpre, Ohio, United States, 45714
Contact: Site Public Contact    800-523-3977    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Adena Regional Medical Center Recruiting
Chillicothe, Ohio, United States, 45601
Contact: Site Public Contact    877-779-7585    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Cleveland Clinic Cancer Center/Fairview Hospital Recruiting
Cleveland, Ohio, United States, 44111
Contact: Site Public Contact    866-223-8100    CancerAnswer@ccf.org   
Principal Investigator: Peter G. Rose         
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Site Public Contact    866-223-8100    CancerAnswer@ccf.org   
Principal Investigator: Peter G. Rose         
Mount Carmel East Hospital Recruiting
Columbus, Ohio, United States, 43213
Contact: Site Public Contact    614-488-2118    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Columbus Oncology and Hematology Associates Inc Recruiting
Columbus, Ohio, United States, 43214
Contact: Site Public Contact    614-488-2118    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Riverside Methodist Hospital Recruiting
Columbus, Ohio, United States, 43214
Contact: Site Public Contact    614-566-4475    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Grant Medical Center Recruiting
Columbus, Ohio, United States, 43215
Contact: Site Public Contact    614-566-4475    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
The Mark H Zangmeister Center Recruiting
Columbus, Ohio, United States, 43219
Contact: Site Public Contact    614-488-2118    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Mount Carmel Health Center West Recruiting
Columbus, Ohio, United States, 43222
Contact: Site Public Contact    614-234-5433    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Doctors Hospital Recruiting
Columbus, Ohio, United States, 43228
Contact: Site Public Contact    614-566-3275    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Delaware Health Center-Grady Cancer Center Recruiting
Delaware, Ohio, United States, 43015
Contact: Site Public Contact    740-615-0227    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Delaware Radiation Oncology Recruiting
Delaware, Ohio, United States, 43015
Contact: Site Public Contact    412-339-5294    Roster@nrgoncology.org   
Principal Investigator: Timothy D. Moore         
Grady Memorial Hospital Recruiting
Delaware, Ohio, United States, 43015
Contact: Site Public Contact    740-615-2403    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Fairfield Medical Center Recruiting
Lancaster, Ohio, United States, 43130
Contact: Site Public Contact    740-687-8863    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
OhioHealth Mansfield Hospital Recruiting
Mansfield, Ohio, United States, 44903
Contact: Site Public Contact    419-526-8018    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Marietta Memorial Hospital Recruiting
Marietta, Ohio, United States, 45750
Contact: Site Public Contact    800-523-3977    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
OhioHealth Marion General Hospital Recruiting
Marion, Ohio, United States, 43302
Contact: Site Public Contact    614-488-2118    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Hillcrest Hospital Cancer Center Recruiting
Mayfield Heights, Ohio, United States, 44124
Contact: Site Public Contact    866-223-8100    CancerAnswer@ccf.org   
Principal Investigator: Peter G. Rose         
Knox Community Hospital Recruiting
Mount Vernon, Ohio, United States, 43050
Contact: Site Public Contact    740-393-9000    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Licking Memorial Hospital Recruiting
Newark, Ohio, United States, 43055
Contact: Site Public Contact    740-348-4000    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Newark Radiation Oncology Recruiting
Newark, Ohio, United States, 43055
Contact: Site Public Contact    614-488-2118    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Southern Ohio Medical Center Recruiting
Portsmouth, Ohio, United States, 45662
Contact: Site Public Contact    614-488-2118    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
Saint Ann's Hospital Recruiting
Westerville, Ohio, United States, 43081
Contact: Site Public Contact    412-339-5294    Roster@nrgoncology.org   
Principal Investigator: Timothy D. Moore         
Genesis Healthcare System Cancer Care Center Recruiting
Zanesville, Ohio, United States, 43701
Contact: Site Public Contact    740-454-5232    sheree@columbusccop.org   
Principal Investigator: Timothy D. Moore         
United States, Pennsylvania
Abington Memorial Hospital Recruiting
Abington, Pennsylvania, United States, 19001
Contact: Site Public Contact    215-481-2402      
Principal Investigator: Mark S. Shahin         
Abington Memorial Hospital-Asplundh Cancer Pavilion Recruiting
Willow Grove, Pennsylvania, United States, 19090
Contact: Site Public Contact    412-339-5294    Roster@nrgoncology.org   
Principal Investigator: Mark S. Shahin         
United States, South Carolina
Saint Francis Hospital Recruiting
Greenville, South Carolina, United States, 29601
Contact: Site Public Contact    864-603-6213    meissa_beckman@bshsi.org   
Principal Investigator: David Griffin         
Saint Francis Cancer Center Recruiting
Greenville, South Carolina, United States, 29607
Contact: Site Public Contact    864-603-6213    meissa_beckman@bshsi.org   
Principal Investigator: David Griffin         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Helen Mackay NRG Oncology

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03660826     History of Changes
Other Study ID Numbers: NCI-2017-01672
NCI-2017-01672 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GY012 ( Other Identifier: NRG Oncology )
NRG-GY012 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Posted: September 7, 2018    Key Record Dates
Last Update Posted: September 24, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma
Adenocarcinoma
Endometrial Neoplasms
Uterine Neoplasms
Carcinoma, Endometrioid
Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Ovarian Neoplasms
Ovarian Diseases
Adnexal Diseases
Gonadal Disorders
Endocrine System Diseases
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Olaparib
Cediranib
Maleic acid
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors