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

NCT02549989 | Completed Phase 2 Results

• 1 other identifier: 15-079
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 6

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.

Conditions

Endometrial Cancer; Recurrent Endometrial Cancer

Keywords

LY3023414; 15-079; Persistent Endometrial Cancer

Outcome Measures

Primary Outcomes (2)

• Clinical Benefit Rate (CBR)

  defined as the percentage of patients with complete response (CR) + partial response (PR) + stable disease (SD) ≥12 weeks from the start of treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  12 weeks from baseline up to a year

• Overall Response Rate

  determined by RECIST 1.1.

  1 year

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  1 year

• Duration of Response (DOR)

  1 year

• Number of Participants Assessed for AE's With PI3K Activated Recurrent/Persistent Endometrial Cancer

  1 year

Study Arms (1)

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.

Drug: LY3023414

Interventions

LY3023414 DRUG

Enrolled patients will take LY3023414 200 mg orally twice a day. Each cycle will be 21 days in duration. Patients will receive study treatment until disease progression, intolerable toxicity, elective withdrawal from the study, study completion, or study termination

LY3023414

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Eli Lilly and Company: collaborator

Study Sites (6)

Memorial Sloan Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

LY3023414

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Results Point of Contact

• Title: Dr. Vicky Makker, MD
• Organization: Memorial Sloan Kettering Cancer Center

makkerv@mskcc.org

646-888-4224

Study Officials

• Vicky Makker, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2015
• First Posted: September 15, 2015
• Study Start: September 1, 2015
• Primary Completion: March 23, 2022
• Study Completion: March 23, 2022
• Last Updated: February 22, 2023
• Results First Posted: February 22, 2023

Record last verified: 2022-03

Locations

US (6)