Brief Title
Study of LY3023414 for the Treatment of Recurrent or Persistent Endometrial Cancer
Official Title
Single-Arm, Open-Label, Phase II Study of LY3023414 for the Treatment of Recurrent or Persistent Endometrial Cancer
Brief Summary
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Clinical Benefit Rate (CBR)
Secondary Outcome
Progression Free Survival (PFS)
Condition
Endometrial Cancer
Intervention
LY3023414
Study Arms / Comparison Groups
LY3023414
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
28
Start Date
September 2015
Completion Date
March 23, 2022
Primary Completion Date
March 23, 2022
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 four 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 bilirubin≤1.5x 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 creatinine≤1.5x 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.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Vicky Makker, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02549989
Organization ID
15-079
Responsible Party
Sponsor
Study Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Eli Lilly and Company
Study Sponsor
Vicky Makker, MD, Principal Investigator, Memorial Sloan Kettering Cancer Center
Verification Date
March 2022