Clinical Trials /

A Study of LY3023414 in Participants With Advanced Cancer

NCT01655225

Description:

The purpose of this study is to find a recommended dose level and schedule of dosing LY3023414 that can safely be taken by participants with advanced or metastatic cancer. The study will also explore the changes to various markers in blood cells and potentially tumor cells. Finally, the study will help document any antitumor activity this drug may have. In Part A of this study, participants with advanced/metastatic cancer (including lymphoma) will receive increasing doses of LY3023414. In Part B, LY3023414 will be explored in different types of cancer, including breast and lung cancer, lymphoma and mesothelioma.

Related Conditions:
  • Breast Carcinoma
  • Cancer
  • Non-Hodgkin Lymphoma
  • Peritoneal Mesothelioma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of LY3023414 in Participants With Advanced Cancer
  • Official Title: A Phase 1 First-in-Human Dose Study of LY3023414 in Patients With Advanced Cancer

Clinical Trial IDs

  • ORG STUDY ID: 13517
  • SECONDARY ID: I6A-MC-CBBA
  • NCT ID: NCT01655225

Conditions

  • Advanced Cancer
  • Metastatic Cancer
  • Non-Hodgkin's Lymphoma
  • Metastatic Breast Cancer
  • Malignant Mesothelioma
  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
LY3023414Part A: LY3023414 Once Daily
MidazolamPart B1 : LY3023414 + Midazolam
FulvestrantPart B2: LY3023414 + Fulvestrant
PemetrexedAlimtaPart B4: LY3023414 + pemetrexed/cisplatin
CisplatinPart B4: LY3023414 + pemetrexed/cisplatin
AbemaciclibLY2835219Part B7: LY3023414 + Abemaciclib + Letrozole
LetrozolePart B7: LY3023414 + Abemaciclib + Letrozole

Purpose

The purpose of this study is to find a recommended dose level and schedule of dosing LY3023414 that can safely be taken by participants with advanced or metastatic cancer. The study will also explore the changes to various markers in blood cells and potentially tumor cells. Finally, the study will help document any antitumor activity this drug may have. In Part A of this study, participants with advanced/metastatic cancer (including lymphoma) will receive increasing doses of LY3023414. In Part B, LY3023414 will be explored in different types of cancer, including breast and lung cancer, lymphoma and mesothelioma.

Trial Arms

NameTypeDescriptionInterventions
Part A: LY3023414 Once DailyExperimentalLY3023414 administered orally once daily (QD) at escalating doses for two 21 day cycles to participants with advanced/metastatic cancer (including lymphoma); participants receiving benefit may continue until disease progression or discontinuation.
  • LY3023414
Part A2: LY3023414 Twice DailyExperimentalLY3023414 administered orally twice daily (BID) at escalating doses for two 21 day cycles to participants with advanced/metastatic cancer (including lymphoma); participants receiving benefit may continue until disease progression or discontinuation.
  • LY3023414
Part B1 : LY3023414 + MidazolamExperimentalLY3023414 administered orally BID for two 21 day cycles to participants with advanced/metastatic cancer; participants receiving benefit may continue until disease progression or discontinuation. Dose based on Part A. 0.2 milligrams (mg) midazolam administered orally once before LY3023414 on Day 1 and once after LY3023414 on Day 15.
  • LY3023414
  • Midazolam
Part B2: LY3023414 + FulvestrantExperimentalLY3023414 administered orally BID for two 28 day cycles to participants with advanced/metastatic breast cancer; participants receiving benefit may continue until disease progression or discontinuation. 500 mg fulvestrant administered IM once every 28 days.
  • LY3023414
  • Fulvestrant
Part B3: LY3023414ExperimentalLY3023414 administered orally BID for two 21 day cycles to participants with malignant mesothelioma; participants receiving benefit may continue until disease progression or discontinuation.
  • LY3023414
Part B4: LY3023414 + pemetrexed/cisplatinExperimentalLY3023414 administered orally BID for two 21 day cycles to participants with malignant mesothelioma; participants receiving benefit may continue until disease progression or discontinuation. 500 mg/m2 pemetrexed and 75 mg/m2 administered IV once every 21 days.
  • LY3023414
  • Pemetrexed
  • Cisplatin
Part B5: LY3023414ExperimentalLY3023414 administered orally BID for two 21 day cycles to participants with indolent non-Hodgkin's lymphoma; participants receiving benefit may continue until disease progression or discontinuation.
  • LY3023414
Part B6: LY3023414ExperimentalLY3023414 administered orally BID for two 21 day cycles to participants with squamous NSCLC; participants receiving benefit may continue until disease progression or discontinuation.
  • LY3023414
Part B7: LY3023414 + Abemaciclib + LetrozoleExperimentalLY3023414 administered orally BID with abemaciclib administered orally BID and letrozole administered orally once a day for two 28 day cycles to participants with breast cancer; participants receiving benefit may continue until disease progression or discontinuation.
  • LY3023414
  • Abemaciclib
  • Letrozole

Eligibility Criteria

        Inclusion Criteria:

          -  Parts A, A2 & B1: Participants must have pathological evidence of a diagnosis of
             advanced and/or metastatic cancer and must be, in the judgment of the investigator, an
             appropriate candidate for experimental therapy

          -  Part B2: Participants must have advanced, recurrent, or metastatic breast cancer that
             is refractory to aromatase inhibitors (AI) with either disease recurrence or disease
             progression; must be hormone receptor positive (HR+) and human epidermal growth factor
             receptor 2 (HER2)-negative; must be of postmenopausal status or beginning ovarian
             suppression with a luteinizing hormone-releasing hormone (LHRH) agonist

          -  Part B3 only: Participants must have malignant pleural or peritoneal mesothelioma

          -  Part B4 only: Participants must have malignant pleural or peritoneal mesothelioma and
             appropriate candidate for treatment with cisplatin/pemetrexed; no prior systemic
             chemotherapy

          -  Part B5 only: Participants must have histologically confirmed diagnosis of B-cell
             iNHL, with histological subtype; prior treatment with ≥2 prior chemotherapy- or
             immunotherapy-based regimens for iNHL

          -  Part B6 only: Participants must have squamous NSCLC; documented evidence of an
             activating molecular aberration of the PI3K/mTOR pathway

          -  Parts B2, B3 & B6 only: Must have adequate tumor tissue sample from archival biopsy
             available, or willingness to undergo a fresh tumor biopsy

          -  Parts B3, B4, B5 & B6: No previous treatment with any PI3K and/or mTOR inhibitor

          -  Part B7: Must have a diagnosis of HR+ and HER2- breast cancer; have locoregionally
             recurrent disease not amenable to resection or radiation therapy with curative intent
             or metastatic disease; no previous treatment or currently receiving 1 of the following
             treatments for locoregionally recurrent or metastatic breast cancer (chemotherapy,
             endocrine therapy, CDK4/6 inhibitor, and PI3K and/or mTOR inhibitor)

          -  Measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in
             Solid Tumors (RECIST Version 1.1), modified RECIST or Revised Response Criteria for
             Malignant Lymphoma

          -  Have adequate organ function, including: Absolute neutrophil count (ANC) at least 1.5
             x 109/Liter (L), platelets at least 100 x 109/L, and hemoglobin at least 8
             grams/deciliter (g/dL); bilirubin no more than 1.5 times upper limits of normal;
             alanine aminotransferase (ALT) and aspartate aminotransferase (AST) no more than 2.0
             times upper limits of normal; Serum creatinine no more than 1.5 times upper limits of
             normal or calculated creatinine clearance >45 milliliters/minute (mL/min)

          -  Have a performance status of at least 1 on the Eastern Cooperative Oncology Group
             (ECOG) scale and life expectancy >6 months

          -  Have discontinued all previous cancer therapies (except nonsteroidal aromatase
             inhibitors for participants in Part B2), and any agents that have not received
             regulatory approval for any indication, for at least 21 days or 5 half lives prior to
             study enrollment, whichever is shorter, and recovered from the acute effects of
             therapy. Participants must have discontinued mitomycin-C or nitrosourea therapy for at
             least 42 days

          -  Are able to swallow capsules

        Exclusion Criteria:

          -  Have serious preexisting medical conditions

          -  Have symptomatic central nervous system (CNS) malignancy (with the exception of
             medulloblastoma) or metastasis (screening not required).

          -  Have known acute or chronic leukemia or current hematologic malignancies (except iNHL
             for patients in Part B5) that, in the judgment of the investigator and sponsor, may
             affect the interpretation of results

          -  Have an active fungal, bacterial, and/or known viral infection

          -  Have a second primary malignancy that in the judgment of the investigator and sponsor
             may affect the interpretation of results (Part B only)

          -  Part B1 only: No concomitant medications that are strong inhibitors or inducers of
             cytochrome P450 3A4 (CYP3A4) or midazolam

          -  Intolerance to any previous treatment with any phosphatidylinositol-3-kinase (PI3K)
             and/or mammalian target of rapamycin (mTOR) inhibitor.

          -  Participants with active alcohol abuse, as determined by the investigator

          -  Have a history of New York Heart Association (NYHA) Class ≥3, unstable angina, or
             myocardial infarction (MI) in 6 months prior to study drug administration

          -  Have QT corrected interval of >450 milliseconds (msec) on screening electrocardiogram
             (ECG)

          -  Have insulin-dependent diabetes mellitus or a history of gestational diabetes
             mellitus.

          -  Part B only: Hypersensitivity to study drugs given in combination with LY3023414
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase 2 dose
Time Frame:Baseline to disease progression or participant discontinuation (estimated 9 weeks)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetics: Maximum concentration (Cmax)
Time Frame:Predose up to 12 hours postdose
Safety Issue:
Description:
Measure:Pharmacokinetics: Time of maximal concentration
Time Frame:Predose up to 12 hours postdose
Safety Issue:
Description:
Measure:Number of participants with tumor response
Time Frame:Baseline to disease progression or participant discontinuation (estimated 9 weeks)
Safety Issue:
Description:
Measure:Potential of LY3023414 to inhibit CYP3A4-mediated metabolism
Time Frame:Baseline through Cycle 1
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eli Lilly and Company

Trial Keywords

  • Advanced Breast Cancer
  • Advanced Lung Cancer
  • Mesothelioma
  • Lymphoma

Last Updated

August 8, 2017