A Study of LY3023414 in Participants With Advanced Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Eli Lilly and Company
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01655225
First received: July 19, 2012
Last updated: June 6, 2014
Last verified: June 2014

July 19, 2012
June 6, 2014
July 2012
September 2014   (final data collection date for primary outcome measure)
Recommended Phase 2 dose [ Time Frame: Baseline to disease progression or participant discontinuation (estimated 9 weeks) ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01655225 on ClinicalTrials.gov Archive Site
  • Pharmacokinetics: Maximum concentration (Cmax) [ Time Frame: Predose up to 12 hours postdose ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Time of maximal concentration [ Time Frame: Predose up to 12 hours postdose ] [ Designated as safety issue: No ]
  • Number of participants with tumor response [ Time Frame: Baseline to disease progression or participant discontinuation (estimated 9 weeks) ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
A Study of LY3023414 in Participants With Advanced Cancer
A Phase 1 First-in-Human Dose Study of LY3023414 in Patients With Advanced Cancer

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, including but not limited to lymphoma, breast cancer, and mesothelioma. 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 cancer and mesothelioma.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Advanced Cancer
  • Metastatic Cancer
  • Lymphoma
  • Metastatic Breast Cancer
  • Malignant Mesothelioma
  • Drug: LY3023414
    Administered orally QD or BID for a 21 day Cycle. Dose of 20 to 600 mg, as determined in Part A.
  • Drug: Midazolam
    0.2 mg administered orally once before LY3023414 on Day 1 and once after LY3023414 on Day 15.
  • Drug: Letrozole
    25 mg administered orally QD.
  • Experimental: Part A: LY3023414 Once Daily
    LY3023414 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.
    Intervention: Drug: LY3023414
  • Experimental: Part A2: LY3023414 Twice Daily
    LY3023414 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.
    Intervention: Drug: LY3023414
  • Experimental: Part B1 : LY3023414 + Midazolam
    LY3023414 administered orally QD or 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 mg midazolam administered orally once before LY3023414 on Day 1 and once after LY3023414 on Day 15.
    Interventions:
    • Drug: LY3023414
    • Drug: Midazolam
  • Experimental: Part B2: LY3023414 + Letrozole
    LY3023414 administered orally QD or BID for two 21 day cycles to participants with advanced/metastatic breast cancer; participants receiving benefit may continue until disease progression or discontinuation. Dose based on Part A. 25 mg Letrozole administered orally QD.
    Interventions:
    • Drug: LY3023414
    • Drug: Letrozole
  • Experimental: Part B3: LY3023414
    LY3023414 administered orally QD or BID for two 21 day cycles to participants with malignant mesothelioma; participants receiving benefit may continue until disease progression or discontinuation. Dose based on Part A.
    Intervention: Drug: LY3023414
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
70
September 2014
September 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Participants must have histological or cytological evidence of a diagnosis of cancer (solid tumor or lymphoma) that is advanced and/or metastatic and must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have failed or for whom standard therapy would not be appropriate
  • Measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) 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

Exclusion Criteria:

  • Have serious preexisting medical conditions
  • Have symptomatic central nervous system (CNS) malignancy (with the exception of medulloblastoma) or metastasis (screening not required). Participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 60 days (screening not required)
  • Have known acute or chronic leukemia or current hematologic malignancies 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, including: human immunodeficiency virus (HIV), or hepatitis A, B or C. Hepatocellular cancer (HCC) participants with chronic viral (B or C) hepatitis are eligible if they retain adequate liver function per Child-Pugh Stage A
  • 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. Treatment with any PI3K and/or mTOR inhibitor must have discontinued at least 5 half-lives prior to study enrollment and participants must have recovered from the acute effects of therapy (treatment-related toxicity resolved to baseline or less than Grade 1). In Part B, no previous treatment with any PI3K and/or mTOR inhibitor is allowed
  • 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 interval corrected using Fridericia's formula (QTcF) of >450 milliseconds (msec) on screening electrocardiogram (ECG)
  • Have insulin-dependent diabetes mellitus or a history of gestational diabetes mellitus. Participants with a type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained by oral anti-diabetics as documented by hemoglobin A1c <7%
Both
18 Years and older
No
Contact: There may be multiple sites in this clinical trial 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559
United States
 
NCT01655225
13517, I6A-MC-CBBA
No
Eli Lilly and Company
Eli Lilly and Company
Not Provided
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
Eli Lilly and Company
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP