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

  • Interventional
  • Recruiting
  • NCT04486352
Eligibility Details Visit Clinicaltrials.gov

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

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.

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

        - Atezolizumab + Trastuzumab emtansine (TDM-1) doublet

        - Atezolizumab + Tiragolumab 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.

Gender
Female

Age Group
18 Years and up

Accepting Healthy Volunteers?
No

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.

         - Measurable disease per RECIST 1.1

         - 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 CDxTM)

         - 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 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

         - 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

         - 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 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 hemorrhage within 6 months

At a Glance

National Government IDNCT04486352

IRB#IRB21-0677

Lead SponsorAlliance Foundation Trials, LLC.

Lead PhysicianJohn Moroney

Collaborator(s)N/A

EligibilityFemale
18 Years and up
Recruiting