A Study of Targeted Agents for Patients With Recurrent or Persistent Endometrial Cancer
NCT ID: NCT04486352
Last Updated: 2025-09-04
Study Results
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Basic Information
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RECRUITING
PHASE1/PHASE2
148 participants
INTERVENTIONAL
2021-10-20
2027-10-31
Brief Summary
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Detailed Description
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This biomarker-driven study provides a platform whereby participants with persistent/recurrent endometrial cancer will be placed into study cohorts evaluating targeted agents selected on the basis of the tumor's specific genomic profile. Prospective participants with persistent and/or recurrent endometrial cancer will be prescreened within 60 days of treatment assignment to have a tumor tissue sample submitted for next-generation sequencing (NGS) using FoundationOne® companion diagnostic (CDx) testing prior to entering screening. If a participant has FoundationOne® CDx testing within five years of enrollment, the previous tumor tissue may be re-analyzed for use in the study. Non-FMI NGS testing may be submitted if approved.
Depending on the cohort assignment per the tumor's biomarker profile, participants will be assigned to the AFT-50A Protocol (atezolizumab+targeted agent) or the AFT-50B Protocol (non-atezolizumab targeted agents). The current study cohorts are as follows:
AFT-50A Cohorts
* Atezolizumab + Bevacizumab doublet - Closed to Accrual
* Atezolizumab + Ipatasertib doublet - Closed to Accrual
* Atezolizumab + Talazoparib doublet
* Atezolizumab + Trastuzumab emtansine (TDM-1) doublet - Closed to Accrual
* Atezolizumab + Tiragolumab doublet - Closed to Accrual
AFT-50B Cohorts
* Inavolisib + Letrozole doublet
* Giredestrant + Abemaciclib doublet
It is anticipated that approximately 20 participants will be enrolled in each study cohort in AFT-50A and 24 participants in each study cohort in AFT-50B, unless otherwise specified for a given cohort due to statistical considerations. Each study cohort will open/close independently of other study cohorts. Once a study cohort reaches the prespecified number of participants, it will be closed to further enrollment, unless an expansion phase is planned.
The study is structured to allow for additional cohorts to be added as the study progresses. These additional study cohorts may be proposed by investigators, but requires approval by the Steering Committee in order to be added to the protocol.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Atezolizumab and Bevacizumab Cohort - Closed to Accrual
Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with no specified gene signatures will be enrolled in this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.
Atezolizumab - 28 Day Cycle
Atezolizumab will be given to participants intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.
Bevacizumab
Bevacizumab will be given to participants intravenously at a dosage of 10mg per participant kilogram every 2 weeks of the 28-day cycle.
Atezolizumab and Ipatasertib Cohort - Closed to Accrual
Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with PIK3CA/AKT1/PTEN-altered tumors will be enrolled in this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.
Atezolizumab - 28 Day Cycle
Atezolizumab will be given to participants intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.
Ipatasertib
Ipatasertib will be given as an orally at a dosage of 400 mg once daily for 21 days of each 28-day cycle.
Atezolizumab and Talazoparib Cohort
Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with tumors that have a ≥16%genomic loss of heterozygosity (LOH) will be assigned to this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.
Atezolizumab - 28 Day Cycle
Atezolizumab will be given to participants intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.
Talazoparib
Talazoparib will be given in an orally at a dosage of 1 mg once daily for each day of the 28-day cycle.
Atezolizumab and Trastuzumab emtansine (TDM-1) Cohort - Closed to Accrual
Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with tumors that with an amplification of ERBB2/HER2 will be assigned to this cohort. Twenty participants will be enrolled. Once twenty participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.
Trastuzumab emtansine
Trastuzumab emtansine be given to participants intravenously at a dosage of 3.6 mg per participant kilogram, on day 1 of each 21-day cycle.
Atezolizumab - 21 Day Cycle
Atezolizumab will be given to participants intravenously at a dosage of 1200 mg on day 1 of each 21-day cycle.
Atezolizumab and Tiragolumab Cohort - Closed to Accrual
Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with tumor type MSI-H and/or tTMB \>=10 mut/mb will be assigned to this cohort. Twenty participants will be enrolled initially. Once twenty participants are enrolled, the cohort may be expanded if a positive signal is shown. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.
Atezolizumab - 28 Day Cycle
Atezolizumab will be given to participants intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.
Tiragolumab
Tiragolumab will be given to participants intravenously at a dosage of 840 mg on day 1 of each 28-day cycle.
Inavolisib and Letrozole Cohort
Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with tumors that with PIK3CA activating mutations in the absence of PTEN loss-of-function alterations or AKT1 activating mutations will be assigned to this cohort. Twenty-four participants will be enrolled. Once twenty-four participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.
Inavolisib
Inavolisib will be given in an orally at a dosage of 9 mg once daily for each day of the 28-day cycle.
Letrozole
Letrozole will be given orally at a dosage of 2.5 mg once daily for each day of the 28-day cycle.
Giredestrant and Abemaciclib
Following the submission of tumor tissue for the FoundationOne® companion diagnostic (F1CDx) test, participants with tumors that are RB1 intact with a local grade 1-2 estrogne receptor positive (ER+) are assigned to this cohort. Twenty-four participants will be enrolled. Once twenty-four participants are enrolled, the cohort will be closed to further enrollment. Participants in this study cohort will commence treatment as specified on Day 1 of each cycle.
Giredestrant
Giredestrant will be given orally at a dosage of 30 mg once daily for each day of the 28-day cycle.
Abemaciclib
Giredestrant will be given orally at a dosage of 150 mg twice daily for each day of the 28-day cycle.
Interventions
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Atezolizumab - 28 Day Cycle
Atezolizumab will be given to participants intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.
Bevacizumab
Bevacizumab will be given to participants intravenously at a dosage of 10mg per participant kilogram every 2 weeks of the 28-day cycle.
Ipatasertib
Ipatasertib will be given as an orally at a dosage of 400 mg once daily for 21 days of each 28-day cycle.
Talazoparib
Talazoparib will be given in an orally at a dosage of 1 mg once daily for each day of the 28-day cycle.
Trastuzumab emtansine
Trastuzumab emtansine be given to participants intravenously at a dosage of 3.6 mg per participant kilogram, on day 1 of each 21-day cycle.
Tiragolumab
Tiragolumab will be given to participants intravenously at a dosage of 840 mg on day 1 of each 28-day cycle.
Atezolizumab - 21 Day Cycle
Atezolizumab will be given to participants intravenously at a dosage of 1200 mg on day 1 of each 21-day cycle.
Inavolisib
Inavolisib will be given in an orally at a dosage of 9 mg once daily for each day of the 28-day cycle.
Letrozole
Letrozole will be given orally at a dosage of 2.5 mg once daily for each day of the 28-day cycle.
Giredestrant
Giredestrant will be given orally at a dosage of 30 mg once daily for each day of the 28-day cycle.
Abemaciclib
Giredestrant will be given orally at a dosage of 150 mg twice daily for each day of the 28-day cycle.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Measurable disease per RECIST 1.1
* Availability of a representative tumor specimen that is suitable for determination of biomarker status via central testing (F1CDx) OR If a patient has a prior F1CDx report from 1 September 2019 or later, those NGS results can be used to determine biomarker status as long as the tumor tissue used in the report was obtained within 5 years prior to prescreening and appropriate signed consent is obtained from the patient.
* Life expectancy \> 12 weeks
* Recovery from effects of recent radiotherapy, surgery, or chemotherapy
Exclusion Criteria
* Other invasive malignancies within the last 5 years, except for non-melanoma skin cancer with no evidence of disease within the past 5 years AND localized breast cancer with previous adjuvant chemotherapy treatment for breast cancer completed \> 5 years ago
* Synchronous primary invasive ovarian or cervical cancer
* Have an active or history of autoimmune disease or immune deficiency
* Have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis based on a screening chest computed tomography (CT) scan
* Active tuberculosis
* Severe infections within 4 weeks
* Have received therapeutic oral or IV antibiotic medication within 2 weeks, except prophylactic antibiotic medication
* Have significant cardiovascular disease
* Are administered treatment with a live attenuated vaccine within 4 weeks, or anticipation of need for such a vaccine during the course of the study
* Have prior allogeneic bone marrow transplantation or solid organ transplant
* History of treatment with systemic immunostimulatory agents (including but not limited to interferons, interleukin-2) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to initiation of study treatment
* History of treatment with systemic immunosuppressive medications within 2 weeks except acute, low-dose, systemic immunosuppressant medications, corticosteroids for chronic obstructive pulmonary disease and asthma, or mineralocorticoids and low-dose corticosteroids for participants with orthostatic hypotension or adrenocortical insufficiency
* Have a history or clinical evidence of any untreated CNS disease, seizures not controlled with standard medical therapy, or history of cerebrovascular accident (stroke), transient ischemic attack or subarachnoid hemorrhage within 6 months
● Prior treatment with T-cell costimulating or immune checkpoint blockade therapies including, but not limited to, CD137 agonists, anti-PD-1, anti-PD-L1, and anti-CTLA-4 therapeutic antibodies
18 Years
FEMALE
No
Sponsors
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Genentech, Inc.
INDUSTRY
Foundation Medicine
INDUSTRY
Pfizer
INDUSTRY
Eli Lilly and Company
INDUSTRY
Alliance Foundation Trials, LLC.
OTHER
Responsible Party
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Locations
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City of Hope Comprehensive Cancer Center
Duarte, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Medstar Georgetown Cancer Institute
Washington D.C., District of Columbia, United States
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States
University of Chicago
Chicago, Illinois, United States
University of Kansas Cancer Center
Westwood, Kansas, United States
Maine Medical Center
Scarborough, Maine, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Minnesota
Minneapolis, Minnesota, United States
Washington University School of Medicine Siteman Cancer Center
St Louis, Missouri, United States
Nebraska Methodist Hospital
Omaha, Nebraska, United States
Englewood Health
Englewood, New Jersey, United States
Atlantic Health Systems/Morristown Medical Center
Morristown, New Jersey, United States
Roswell Park
Buffalo, New York, United States
Weill Cornell Medicine
New York, New York, United States
Duke University Cancer Center
Durham, North Carolina, United States
University of Oklahoma Health Stephenson Cancer Center
Oklahoma City, Oklahoma, United States
Providence Portland Cancer Institute
Portland, Oregon, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Lifespan - Rhode Island Hospital
Providence, Rhode Island, United States
Baptist Memorial Hospital
Memphis, Tennessee, United States
Countries
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Central Contacts
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Facility Contacts
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Edwin Alvarez, MD
Role: primary
Ebony Hoskins, MD
Role: primary
Brian Slomovitz, MD
Role: primary
John Moroney, MD
Role: primary
Andrea Jewell, MD
Role: primary
Leslie Bradford, MD
Role: primary
Joyce Liu, MD, MPH
Role: primary
Britt Erickson, MD
Role: primary
Brent Tierney, MD
Role: primary
Nana Tchabo, MD
Role: primary
Evelyn Cantillo, MD, MPH
Role: primary
Angeles Alvarez Secord, MD
Role: primary
Debra Richardson, MD
Role: primary
Christopher Darus, MD
Role: primary
Don Dizon, MD
Role: primary
References
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Related Links
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Other Identifiers
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AFT-50
Identifier Type: -
Identifier Source: org_study_id
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