A Study of LY3023414 in Participants With Advanced Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 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: September 22, 2014
Last verified: September 2014
  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.


Condition Intervention Phase
Advanced Cancer
Metastatic Cancer
Non-Hodgkin's Lymphoma
Metastatic Breast Cancer
Malignant Mesothelioma
Non-small Cell Lung Cancer
Drug: LY3023414
Drug: Midazolam
Drug: Fulvestrant
Drug: Pemetrexed
Drug: Cisplatin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 First-in-Human Dose Study of LY3023414 in Patients With Advanced Cancer

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Recommended Phase 2 dose [ Time Frame: Baseline to disease progression or participant discontinuation (estimated 9 weeks) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]
  • Potential of LY3023414 to inhibit CYP3A4-mediated metabolism [ Time Frame: Baseline through Cycle 1 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 130
Study Start Date: July 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: LY3023414
Administered orally QD or BID for a 21 day Cycle. Dose of 20 to 600 mg, as determined in Part A.
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.
Drug: LY3023414
Administered orally QD or BID for a 21 day Cycle. Dose of 20 to 600 mg, as determined in Part A.
Experimental: Part B1 : LY3023414 + Midazolam
LY3023414 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 mg midazolam administered orally once before LY3023414 on Day 1 and once after LY3023414 on Day 15.
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.
Experimental: Part B2: LY3023414 + Fulvestrant
LY3023414 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.
Drug: LY3023414
Administered orally QD or BID for a 21 day Cycle. Dose of 20 to 600 mg, as determined in Part A.
Drug: Fulvestrant
500 mg administered IM on Day 1 and Day 15 in cycle 1 and Day 1 every 28 days for additional cycles.
Experimental: Part B3: LY3023414
LY3023414 administered orally BID for two 21 day cycles to participants with malignant mesothelioma; participants receiving benefit may continue until disease progression or discontinuation.
Drug: LY3023414
Administered orally QD or BID for a 21 day Cycle. Dose of 20 to 600 mg, as determined in Part A.
Experimental: Part B4: LY3023414 + pemetrexed/cisplatin
LY3023414 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.
Drug: LY3023414
Administered orally QD or BID for a 21 day Cycle. Dose of 20 to 600 mg, as determined in Part A.
Drug: Pemetrexed
500 mg/m2 administered IV once on Day 1 every 21 days
Other Name: Alimta
Drug: Cisplatin
75 mg/m2 administered IV once on Day 1 every 21 days
Experimental: Part B5: LY3023414
LY3023414 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.
Drug: LY3023414
Administered orally QD or BID for a 21 day Cycle. Dose of 20 to 600 mg, as determined in Part A.
Experimental: Part B6: LY3023414
LY3023414 administered orally BID for two 21 day cycles to participants with squamous NSCLC; participants receiving benefit may continue until disease progression or discontinuation.
Drug: LY3023414
Administered orally QD or BID for a 21 day Cycle. Dose of 20 to 600 mg, as determined in Part A.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01655225

Contacts
Contact: There may be multiple sites in this clinical trial 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

Locations
United States, New York
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
New York, New York, United States, 10065
Contact: Eli Lilly         
United States, Oklahoma
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Eli Lilly         
United States, Pennsylvania
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Eli Lilly         
United States, Tennessee
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Nashville, Tennessee, United States, 37203
Contact: Eli Lilly         
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01655225     History of Changes
Other Study ID Numbers: 13517, I6A-MC-CBBA
Study First Received: July 19, 2012
Last Updated: September 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Advanced Breast Cancer
Advanced Lung Cancer
Mesothelioma
Lymphoma

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Lymphoma
Lymphoma, Non-Hodgkin
Mesothelioma
Neoplasm Metastasis
Neoplasms
Neoplasms, Mesothelial
Adenoma
Breast Diseases
Bronchial Neoplasms
Carcinoma, Bronchogenic
Immune System Diseases
Immunoproliferative Disorders
Lung Diseases
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplastic Processes
Pathologic Processes
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Skin Diseases
Thoracic Neoplasms
Cisplatin
Fulvestrant
Midazolam

ClinicalTrials.gov processed this record on October 30, 2014