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Atezolizumab and Bevacizumab in Treating Patients with Advanced, Recurrent, or Refractory Endometrial Cancer

Trial Status: Active

This phase II trial studies how well atezolizumab and bevacizumab work in treating patients with endometrial cancer that has spread to other places in the body, has come back, or does not respond to treatment. Immunotherapy with atezolizumab and bevacizumab, may induce changes in body’s immune system and may interfere with the ability of tumor cells to grow and spread.

Inclusion Criteria

  • Histologic or cytologic diagnosis of endometrial carcinoma (including endometrioid, serous, mixed adenocarcinoma, clear-cell carcinoma, or carcinosarcoma)
  • Evidence that the endometrial cancer is advanced, recurrent, or persistent and has relapsed or is refractory to curative therapy or established treatments
  • At least 1 prior platinum-based chemotherapeutic regimen, but not more than 2 prior chemotherapeutic regimens, for management of endometrial carcinoma. Prior treatment may include chemotherapy, and/or consolidation/maintenance therapy
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded). Each lesion must be >= 10 mm in long axis when measured by computed tomography (CT), magnetic resonance imaging (MRI), or caliper measurement by clinical exam. Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • Female patients who: * Are postmenopausal for at least 1 year before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method at the same time, from the time of signing the informed consent through 90 days (or longer, as mandated by local labeling [eg, United States Prescribing Information (USPI), Summary of Product Characteristics (SmPC), etc.]) after the last dose of study drug, OR * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject
  • Absolute neutrophil count (ANC) >= 1500/uL (within 4 weeks before the first dose of study drug)
  • Platelet count >= 100,000/uL (within 4 weeks before the first dose of study drug)
  • Hemoglobin >= 9 g/dL (within 4 weeks before the first dose of study drug)
  • Total bilirubin must be < 1.5 x the upper limit of normal (ULN) (within 4 weeks before the first dose of study drug)
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be =< 3 x the upper limit of the normal range (within 4 weeks before the first dose of study drug). AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to the presence of metastatic disease in liver
  • Creatinine =< 1.5 x ULN or creatinine clearance >= 50 mL/min/1.73 m^2 based either on Cockcroft-Gault estimate or based on a 12- or 24-hour urine collection (within 4 weeks before the first dose of study drug) * Urine protein < 2.0. All patients with >= 2 + protein on dipstick urinalysis at baseline must undergo a urine protein-to-creatinine ratio and/or 24-hour urine collection and demonstrate < 1.0 of protein
  • Urine protein: creatinine ratio (UPCR) =< 1.0 (For UPCR > 1, a 24-hour urine protein should be obtained and the level should be < 1000 mg) (within 4 weeks before the first dose of study drug)
  • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (within 4 weeks before the first dose of study drug) (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low molecular-weight heparin or warfarin, should be on a stable dose) (within 4 weeks before the first dose of study drug)
  • Able to understand and willing to sign the informed consent form and the written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
  • Must have ability to comply with the study protocol, in the investigator’s judgment
  • Patients microsatellite instability (MSI) status must be known (via immunohistochemistry)
  • Patients should have archival tumor tissue available or agree to have pre-treatment tumor biopsy if no archival tissue is available for correlative studies
  • Life expectancy of greater than 12 weeks

Exclusion Criteria

  • Positive serum pregnancy test during the screening period or a positive urine pregnancy test on day 1 before first dose of study drug. Women who are lactating and breast feeding are not eligible
  • Previous treatment with anti−PD-1, or anti−PD-L1 therapeutic antibody
  • History of auto-immune disorders (systemic lupus erythematosus [SLE], sarcoidosis, rheumatoid arthritis [RA], Crohn’s)
  • Initiation of treatment with systemic corticosteroids (either IV or oral steroids, excluding inhalers) within 1 week before administration of the first dose of study drug
  • Sensory or motor neuropathy >= grade 2
  • Patients with symptomatic, untreated central nervous system (CNS) metastasis * Patients with a history of treated CNS lesions are eligible, provided that all of the following criteria are met: ** Measurable disease, per RECIST version (v)1.1, must be present outside the CNS ** The patient has no history of intracranial hemorrhage or spinal cord hemorrhage ** Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord) ** There is no evidence of interim progression between completion of CNS directed therapy and the screening brain scan ** The patient has not received stereotactic radiotherapy within 7 days prior to initiation of study treatment or whole-brain radiotherapy within 14 days prior to initiation of study treatment ** The patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted * Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan
  • Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active CNS disease, severe cardiac disease, bleeding diathesis, active infection, or any other condition that could compromise participation of the patient in the study
  • Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • Patients who have had investigational therapy, chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier; however, the following therapies are allowed: * Hormone-replacement therapy or oral contraceptives * Herbal therapy > 1 week prior to cycle 1, day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1) * Palliative radiotherapy for bone metastases > 2 weeks prior to cycle 1, day 1
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks or five half-lives of the drug (whichever is shorter) prior to cycle 1, day 1
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, compounds similar to bevacizumab or atezolizumab, or Chinese hamster ovary products
  • Major surgical procedure within 28 days prior to cycle 1, day 1 or anticipation of need for a major surgical procedure during the course of the study
  • History of abdominal/pelvic fistula, gastrointestinal perforation and/or intraabdominal abscess within 6 months prior to day 1. Serious or non-healing wound, active ulcer or bone fracture
  • Immunocompromised patients and subjects known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy. NOTE: Subjects known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial

Oklahoma

Oklahoma City
Stephenson Cancer Center
Status: ACTIVE
Contact: Camille Gunderson
Phone: 405-271-8707

PRIMARY OBJECTIVES:

I. To estimate the objective tumor response (complete response + partial response) in women with recurrent endometrial cancer upon treatment with a combination of atezolizumab + bevacizumab.

SECONDARY OBJECTIVES:

I. To estimate progression-free survival (PFS) and overall survival (OS) of patients with recurrent or persistent endometrial cancer treated with atezolizumab and bevacizumab.

II. To identify the safety of combination atezolizumab and bevacizumab using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria.

III. To estimate response using immune related response criteria (irRC) in patients receiving atezolizumab and bevacizumab.

EXPLORATORY OBJECTIVES:

I. To measure changes in blood and tumor immune profile by ribonucleic (RNA) expression at pre-treatment and at response or end-of-therapy to bevacizumab and atezolizumab via a nanostring platform.

II. To compare tumor mutational burden (TMB) and The Cancer Genome Atlas (TCGA) subgroup (microsatellite instability [MSI], PolE, p53, NSMP [no specific molecular profile]) in patients who achieve a response with bevacizumab/atezolizumab combination therapy versus those who do not have an objective response.

III. To correlate tumor infiltrating lymphocytes (TILs) and PD-L1 positivity via hematoxylin and eosin (H&E) staining and quantitative immunofluorescence (QIF) and mutation associated neoantigen (MANA, as measured by MANA specific T cell receptor sequencing) in patients who achieve a response in comparison to those who do not.

OUTLINE:

Patients receive atezolizumab intravenously (IV) over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 6 months and then every 3 months for 3 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Stephenson Cancer Center

Principal Investigator
Camille Gunderson

  • Primary ID OU-SCC-GEN-001
  • Secondary IDs NCI-2019-01623
  • Clinicaltrials.gov ID NCT03526432