RecruitingPhase 1Phase 2NCT04486352

A Study of Targeted Agents for Patients With Recurrent or Persistent Endometrial Cancer

A Phase IB/II Multi-Cohort Study of Targeted Agents and/or Immunotherapy With Atezolizumab for Patients With Recurrent or Persistent Endometrial Cancer


Sponsor

Alliance Foundation Trials, LLC.

Enrollment

148 participants

Start Date

Oct 20, 2021

Study Type

INTERVENTIONAL

Conditions

Summary

This is a Phase IB/II multi-cohort study designed to evaluate the efficacy and safety of targeted agents with or without cancer immune checkpoint therapy with atezolizumab in participant with recurrent and/or persistent endometrial cancer. The main protocol provides a platform for genomic screening with homogeneous basic eligibility criteria in order to direct study participants into biomarker-matched study cohorts consisting of testing targeted agents.


Eligibility

Sex: FEMALEMin Age: 18 Years

Inclusion Criteria5

  • Recurrent or persistent endometrial carcinoma which has progressed or recurred after at least 1, but no more than 2, prior lines of therapy. Prior hormonal therapies (e.g., tamoxifen, aromatase inhibitors) will not count toward the prior regimen limit. Chemotherapy given in conjunction with radiotherapy as a radiosensitizer will be counted as a systemic therapeutic regimen.
  • 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 Criteria15

  • Endometrial tumors with the following histologies: squamous carcinomas, sarcomas
  • 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

Interventions

DRUGAtezolizumab - 28 Day Cycle

Atezolizumab will be given to participants intravenously at a dosage of 1680 mg on day 1 of each 28-day cycle.

DRUGBevacizumab

Bevacizumab will be given to participants intravenously at a dosage of 10mg per participant kilogram every 2 weeks of the 28-day cycle.

DRUGIpatasertib

Ipatasertib will be given as an orally at a dosage of 400 mg once daily for 21 days of each 28-day cycle.

DRUGTalazoparib

Talazoparib will be given in an orally at a dosage of 1 mg once daily for each day of the 28-day cycle.

DRUGTrastuzumab 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.

DRUGTiragolumab

Tiragolumab will be given to participants intravenously at a dosage of 840 mg on day 1 of each 28-day cycle.

DRUGAtezolizumab - 21 Day Cycle

Atezolizumab will be given to participants intravenously at a dosage of 1200 mg on day 1 of each 21-day cycle.

DRUGInavolisib

Inavolisib will be given in an orally at a dosage of 9 mg once daily for each day of the 28-day cycle.

DRUGLetrozole

Letrozole will be given orally at a dosage of 2.5 mg once daily for each day of the 28-day cycle.

DRUGGiredestrant

Giredestrant will be given orally at a dosage of 30 mg once daily for each day of the 28-day cycle.

DRUGAbemaciclib

Giredestrant will be given orally at a dosage of 150 mg twice daily for each day of the 28-day cycle.


Locations(21)

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

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NCT04486352


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