Clinical Trials /

Study of LY3023414 for the Treatment of Recurrent or Persistent Endometrial Cancer

NCT02549989

Description:

The purpose of this study is to determine the effectiveness of LY3023414 in treating the participants type of cancer and to determine the types and severity of side effects caused by treatment with LY3023414.

Related Conditions:
  • Endometrial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Study of <span class="go-doc-concept go-doc-intervention">LY3023414</span> for the Treatment of Recurrent

Title

  • Brief Title: Study of LY3023414 for the Treatment of Recurrent
  • Official Title: Single-Arm, Open-Label, Phase II Study of LY3023414 for the Treatment of Recurrent
  • Clinical Trial IDs

    NCT ID: NCT02549989

    ORG ID: 15-079

    Trial Conditions

    Endometrial Cancer

    Recurrent Endometrial Cancer

    Trial Interventions

    Drug Synonyms Arms
    LY3023414 LY3023414

    Trial Purpose

    The purpose of this study is to determine the effectiveness of LY3023414 in treating the
    participants type of cancer and to determine the types and severity of side effects caused
    by treatment with LY3023414.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    LY3023414 Experimental This is an MSKCC investigator-initiated, single-center, non-randomized, open-label, phase II study to evaluate the activity of LY3023414 dosed at the RP2D of 200 mg orally twice daily in patients with recurrent or persistent endometrial cancer. LY3023414

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must have recurrent or persistent endometrial carcinoma Patients with the
    following histologic epithelial cell types are eligible: endometrioid adenocarcinoma,
    serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed
    epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous
    adenocarcinoma, squamous cell carcinoma, transitional cell carcinoma, and
    carcinosarcoma.

    - Age 18 years

    - Patients must have had at least one but no more than two prior chemotherapeutic
    regimens for management of endometrial carcinoma (including neo-adjuvant and/or
    adjuvant chemotherapy). Initial treatment may include chemotherapy, chemotherapy and
    radiation therapy, and/or consolidation/maintenance therapy. Chemotherapy
    administered in conjunction with primary radiation as a radio-sensitizer WILL be
    counted as a systemic chemotherapy regimen.

    - Patients tumors must have known PI3K pathway activation defined as EITHER of the
    following on a CLIA-approved molecular diagnostics test:

    - Genomic alteration resulting in loss of PTEN function including a) whole or partial
    gene deletion, frame shift mutations, or non-sense mutations. Missense mutations in
    PTEN will not be considered qualifying.

    - A previously characterized activating mutation in any component of the pathway
    including: PIK3CA, AKT1, PIK3R1, PIK3R2, mTOR

    - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

    - Resolution of adverse effects of recent surgery, radiotherapy, or chemotherapy to
    Grade 1 prior to first study treatment (with the exception of alopecia or
    neuropathy).

    - Patients must have measurable disease. Measurable disease is defined by RECIST
    (version 1.1). Measurable disease is defined as at least one lesion that can be
    accurately measured in at least one dimension (longest diameter to be recorded). Each
    lesion must be 10 mm when measured by CT, MRI or caliper measurement by clinical
    exam; or 20 mm when measured by chest x-ray. Lymph nodes must be 15 mm in short
    axis when measured by CT or MRI.

    - No active infection requiring antibiotics (with the exception of uncomplicated
    urinary tract infection).

    - Any other prior therapy directed at the malignant tumor, including immunologic agents
    and radiotherapy, must be discontinued at least 2 weeks prior to first study
    treatment.

    - Adequate hematologic defined by the following laboratory results obtained within 14
    days prior to first study treatment:

    - Absolute neutrophil count (ANC) 1500/10^9dL

    - Platelet count 100,000/10^9dL

    - Hemoglobin 9.0 g/dL

    - Adequate hepatic function defined by the following laboratory results obtained within
    14 days prior to first study treatment:

    - Total bilirubin1.5x the upper limit of normal (ULN)

    - AST and ALT 3.0x ULN (unless the patient has Gilbert's Syndrome, in which case AST
    and ALT 5.0x ULN is permitted

    - Albumin 3.5 g/dL

    - Adequate renal function defined by the following laboratory results obtained within
    14 days prior to first study treatment:

    - Serum creatinine1.5x ULN OR creatinine clearance 50 mL/min on the basis of the
    Cockcroft-Gault glomerular filtration rate estimation

    - For all patients (regardless of known diabetes) the following is required at
    screening: Fasting blood glucose 135 mg/dL (7.49 mmol/L) and HbA1c 7.0%

    - For patients of childbearing potential, agreement to use two effective forms of
    contraception (e.g., surgical sterilization, a reliable barrier method, birth control
    pills, or contraceptive hormone implants) and to continue its use for the duration of
    the study and for 30 days after the last LY3023414 dose.

    - Patients must have been enrolled, or agree to consent to the companion genomic
    profiling study MSKCC IRB# 12-245.

    - Willingness to sign written informed consent to this study.

    Exclusion Criteria:

    - Patients with known concurrent activating RAS/RAF mutation or loss of function
    mutation or deletion in NF1 of NF2 resulting in MAP kinase pathway activation.
    Patients are not required to be evaluated for these alterations if not already
    performed.

    - Patients with diabetes requiring insulin or requiring more than one non-insulin
    hypoglycemia agents.

    - Patients previously treated with an mTOR, AKT, or PI3K inhibitor (including but not
    limited to GDC-0941, GDC-0980, BEZ235, BKM120, LY294002, PIK-75, TGX-221, XL147,
    XL765, SF1126, PX-866, D-87503, D-106669, GSK615, CAL101, everolimus, temsirolimus,
    and ridaforolimus). For agents not listed, the Study PI or Co-PI will make a
    determination.

    - History of myocardial infarction or unstable angina within 6 months prior to first
    study treatment.

    - New York Heart Association Class II or greater congestive heart failure.

    - Patients with a QTcF interval of >450 msec on screening electrocardiogram (ECG) Note:
    If >450 msec on the first ECG, 2 additional ECGs can be ordered same day and then the
    average may be used to determine eligibility.

    - History of malabsorption syndrome or other condition that would interfere with
    enteral absorption.

    - Inability or unwillingness to swallow pills

    - Clinically significant history of liver disease, including cirrhosis and current
    alcohol abuse.

    - Active hepatitis B or hepatitis C infection. Patients with previously resolved
    hepatitis B infection are eligible. Presence of positive test results for hepatitis B
    infection who have resolved the infection (defined by being positive for HB surface
    antibody (anti-HBs) and polymerase chain reaction (PCR) assay is negative for HBV
    DNA) are eligible. Patients positive for HCV antibody are eligible only if testing
    for HCV RNA is negative.

    - Known HIV infection.

    - Need for current chronic corticosteroid therapy ( 10 mg of prednisone per day or an
    equivalent dose of other anti-inflammatory corticosteroids)

    - Pregnancy, lactation, or breastfeeding

    - Current severe, uncontrolled systemic disease (e.g., clinically significant
    cardiovascular, pulmonary, or metabolic disease)

    - Major surgical procedure or significant traumatic injury within 28 days prior to Day
    1 or anticipation of the need for major surgery during the course of study treatment.

    - Known untreated or active central nervous system (CNS) metastases (progressing or
    requiring anticonvulsants or corticosteroids for symptomatic control). Patients with
    a history of treated CNS metastases are eligible, provided that they meet all of the
    following criteria:

    - Presence of measurable disease outside the CNS

    - No radiographic evidence of worsening upon the completion of CNS-directed therapy and
    no evidence of interim progression between the completion of CNS-directed therapy and
    the screening radiographic study

    - No history of intracranial hemorrhage or spinal cord hemorrhage

    - No ongoing requirement for dexamethasone as therapy for CNS disease (anticonvulsants
    at a stable dose are allowed)

    - Absence of leptomeningeal disease

    - Inability to comply with study and follow-up procedures.

    - Any other disease, metabolic dysfunction, physical examination finding, or clinical
    laboratory finding that, in the investigator's opinion, gives reasonable suspicion of
    a disease or condition that contraindicates the use of an investigational drug or
    that may affect the interpretation of the results or render the patient at high risk
    from treatment complications.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    clinical benefit rate (CBR)

    overall response rate

    Secondary Outcome Measures

    progression free survival (PFS)

    Trial Keywords

    LY3023414

    15-079

    Persistent Endometrial Cancer