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A Study of Targeted Agents With Atezolizumab for Patients With Recurrent or Persistent Endometrial Cancer (EndoMAP)

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ClinicalTrials.gov Identifier: NCT04486352
Recruitment Status : Recruiting
First Posted : July 24, 2020
Last Update Posted : November 11, 2021
Sponsor:
Collaborators:
Genentech, Inc.
Foundation Medicine
Pfizer
Information provided by (Responsible Party):
Alliance Foundation Trials, LLC.

Brief Summary:
This is a Phase IB/II multi-cohort study designed to evaluate the efficacy and safety of targeted agents plus cancer immune checkpoint therapy with atezolizumab for patients 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 subjects into biomarker-matched study cohorts consisting of testing targeted agents with atezolizumab.

Condition or disease Intervention/treatment Phase
Endometrial Cancer Drug: Atezolizumab Drug: Bevacizumab Drug: Ipatasertib Drug: Talazoparib Phase 1 Phase 2

Detailed Description:

This is a Phase IB/II multi-cohort study designed to evaluate the efficacy and safety of targeted agents plus cancer immune checkpoint therapy with atezolizumab in patients with recurrent and/or persistent endometrial cancer.

This biomarker-driven study provides a platform whereby patients with persistent/recurrent endometrial cancer will be placed into study cohorts evaluating atezolizumab plus a targeted agent selected on the basis of the tumor's specific genomic profile. Prospective patients 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.

Based on the FoundationOne® results, patients will be assigned to a study cohort with a targeted therapy + atezolizumab. The current study cohorts are as follows:

  • Atezolizumab + Bevacizumab doublet
  • Atezolizumab + Ipatasertib doublet
  • Atezolizumab + Talazoparib doublet

It is anticipated that 20 patients will be enrolled in each study cohort. Each study cohort will open/close independently of other study cohorts. Once a study cohort reaches 20 patients, it will be closed to further enrollment.

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IB/II Multi-Cohort Study of Targeted Agents With Atezolizumab for Patients With Recurrent or Persistent Endometrial Cancer
Actual Study Start Date : October 20, 2021
Estimated Primary Completion Date : October 2025
Estimated Study Completion Date : October 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Atezolizumab and Bevacizumab Cohort
Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, patients with no specified gene signatures will be enrolled in this cohort. Twenty patients will be enrolled. Once twenty patientsare enrolled, the cohort will be closed to further enrollment. Patients in this study cohort will commence treatment as specified on Day 1 of each cycle.
Drug: Atezolizumab
Atezolizumab would be given to patients intravenously at a dosage of 1680 mg every 4 weeks on a 28-day cycle.
Other Names:
  • Tecentriq
  • L01XC32

Drug: Bevacizumab
Bevacizumab would be given to patients intravenously at a dosage of 10mg per patient kilogram every 2 weeks of the 28-day cycle.
Other Names:
  • Avastin
  • L01XC07

Experimental: Atezolizumab and Ipatasertib Cohort
Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, patients with PIK3CA/AKT1/PTEN-altered tumors will be enrolled in this cohort. Twenty patients will be enrolled. Once twenty patients are enrolled, the cohort will be closed to further enrollment. Patients in this study cohort will commence treatment as specified on Day 1 of each cycle.
Drug: Atezolizumab
Atezolizumab would be given to patients intravenously at a dosage of 1680 mg every 4 weeks on a 28-day cycle.
Other Names:
  • Tecentriq
  • L01XC32

Drug: Ipatasertib
Ipatasertib will be given as an oral tablet at a dosage of 400 mg once daily for 21 days of each 28-day cycle.
Other Names:
  • RG7440
  • GDC-0068

Experimental: Atezolizumab and Talazoparib Cohort
Following the submission of tumor tissue to Foundation Medicine for the FoundationOne® assay, patients with tumors that have a ≥16%genomic loss of heterozygosity (LOH) will be assigned to this cohort. Twenty patients will be enrolled. Once twenty patients are enrolled, the cohort will be closed to further enrollment. Patients in this study cohort will commence treatment as specified on Day 1 of each cycle.
Drug: Atezolizumab
Atezolizumab would be given to patients intravenously at a dosage of 1680 mg every 4 weeks on a 28-day cycle.
Other Names:
  • Tecentriq
  • L01XC32

Drug: Talazoparib
Talazoparib will be given in an oral tablet at a dosage of 1 mg once daily for each day of the 28-day cycle.
Other Names:
  • Talzenna
  • L01XX60




Primary Outcome Measures :
  1. Investigator-assessed overall response rate (ORR) of each biomarker cohort [ Time Frame: 48 Months ]
    Overall response rate for each biomarker cohort is defined as the proportion of patients achieving a complete (CR) or partial (PR) response on two consecutive occasions at least 4 weeks apart, as determined by the investigator from tumor assessments per RECIST v1.1.


Secondary Outcome Measures :
  1. Relative proportion of patients in each biomarker cohort who remain progression-free for at least 6 months compared to that from historical control studies [ Time Frame: 6 Months per cohort ]
    PFS rate at 6 months is defined as the proportion of patients who have not experienced disease progression or death from any cause at 6 months, as determined by the investigator according to RECIST v1.1

  2. Investigator assessed disease-control rate of each biomarker cohort [ Time Frame: 48 Months ]
    Disease-control rate is defined as the proportion of patients achieving either stable disease, complete response, or partial response.

  3. Duration of response for patients in each biomarker cohort who achieve a complete or partial response. [ Time Frame: 48 Months ]
    Duration of response is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.

  4. Overall survival (OS) rates of patients in each biomarker cohort after 24 months [ Time Frame: 24 Months per cohort ]
    24-month overall survival rate is defined as the proportion of patients who have not experienced death from any cause at 24 months.


Other Outcome Measures:
  1. Safety of each biomarker cohort: adverse events [ Time Frame: 48 Months ]
    The incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0), as well as summaries of changes in clinically relevant laboratory test results, changes in vital signs, and study treatment exposures for each biomarker cohort



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

Key Inclusion Criteria:

  • 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
  • Formalin-fixed, paraffin-embedded tumor tissue, a specimen as proximal to the current recurrence as possible, must be submitted to the Central Lab for molecular testing (FoundationOne® assay).
  • Life expectancy > 12 weeks
  • Recovery from effects of recent radiotherapy, surgery, or chemotherapy

Key Exclusion Criteria:

  • 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
  • localized breast cancer with previous adjuvant chemotherapy treatment for breast cancer completed > 5 years ago
  • Have 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
  • Have active tuberculosis
  • Have 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
  • 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
  • Have 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
  • Have 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 patients 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

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): NCT04486352


Contacts
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Contact: Quality Management and Compliance 617-732-8727 ClinicalTrials.Queries@alliancefoundationtrials.org

Locations
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United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: Daphne Stewart         
Principal Investigator: Daphne Stewart, MD, MS         
University of San Francisco Medical Center Not yet recruiting
San Francisco, California, United States, 94143
Contact: Edwin Alvarez, MD         
Principal Investigator: Edwin Alvarez, MD         
United States, Florida
Mount Sinai Comprehensive Cancer Center Not yet recruiting
Miami Beach, Florida, United States, 33140
Contact: Brian Slomovitz, MD         
Principal Investigator: Brian Slomovitz, MD         
United States, Illinois
University of Chicago Not yet recruiting
Chicago, Illinois, United States, 60637
Contact: John Moroney, MD         
Principal Investigator: John Moroney, MD         
United States, Massachusetts
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02125
Contact: Joyce Liu, MD, MPH         
Principal Investigator: Joyce Liu, MD, MPH         
United States, Missouri
Washington University School of Medicine Siteman Cancer Center Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: Premal Thaker, MD, MS         
Principal Investigator: Premal Thaker, MD, MS         
United States, New Jersey
Englewood Health Recruiting
Englewood, New Jersey, United States, 07631
Contact: Nimesh Nagarsheth, MD         
Principal Investigator: Nimesh Nagarsheth, MD         
Atlantic Health Systems/Morristown Medical Center Not yet recruiting
Morristown, New Jersey, United States, 07960
Contact: Nana Tchabo, MD         
Principal Investigator: Nana Tchabo, MD         
United States, New York
Weill Cornell Medicine Not yet recruiting
New York, New York, United States, 10065
Contact: Evelyn Cantillo, MD, MPH         
Principal Investigator: Evelyn Cantillo, MD, MPH         
United States, North Carolina
Duke University Cancer Center Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Angeles Alvarez Secord, MD         
Principal Investigator: Angeles Alvarez Secord, MD         
Sponsors and Collaborators
Alliance Foundation Trials, LLC.
Genentech, Inc.
Foundation Medicine
Pfizer
Additional Information:
Publications:

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Responsible Party: Alliance Foundation Trials, LLC.
ClinicalTrials.gov Identifier: NCT04486352    
Other Study ID Numbers: AFT-50
First Posted: July 24, 2020    Key Record Dates
Last Update Posted: November 11, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Bevacizumab
Atezolizumab
Talazoparib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action