A Study of LY3039478 in Participants With Advanced Cancer

Phase 1

Completed

• Conditions: Neoplasms; Lymphoma; Neoplasm Metastasis
• Interventions: Drug: LY3039478; Drug: Prednisone

• Registration Number: NCT01695005
• Lead Sponsor: Eli Lilly and Company

Brief Summary

The purpose of this study is to find a recommended dose level of LY3039478 that can safely be taken by participants with advanced cancer or cancer that has spread to other parts of the body, including but not limited to lymphoma. The study will also explore changes to various markers in blood cells and tissue. Finally, the study will help to document any tumor activity this drug may have.

Detailed Description

In Part A of this study, participants with advanced/metastatic cancer (including lymphoma) will receive increasing doses of LY3039478 to define the dose level for Part B, C, D and E. In Part B, C, D and E LY3039478 will be explored at a predefined fixed dose level. Participants in Part B and D must have a defined alteration in a certain molecular pathway. Enrollment of participants in Part B, C, D and E will start once Part A is completed. In Part F participants will receive increasing doses of LY3039478 in combination with prednisone to define the maximum tolerated dose level.

Study Timeline

• Study First Submitted: 2012-09-24
• Study First Submitted QC: 2012-09-24
• Study First Posted: 2012-09-27
• Study Start: 2012-10
• Primary Completion: 2018-06-26
• Study Completion: 2018-06-26
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-06
• Last Update Posted: 2018-08-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 237

Inclusion Criteria

• For all parts: The participant must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have failed to provide clinical benefit for their advanced or metastatic cancer.

• For Dose Escalation (Part A): The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced or metastatic.

• For Part B: All participants must have a histological evidence of their advanced or metastatic cancer and prescreened alterations in a defined pathway.

• For Part C: All participants must have histological evidence of advanced or metastatic specific subtypes of soft tissue sarcoma.

• For Part D: All participants must have histological evidence of advanced or metastatic cancer and prescreened alterations in a defined pathway.

• Cohort 1: Participants must have triple negative breast cancer.

• Cohort 2: Participants must have hepatocellular carcinoma (HCC). These participants should have Child-Pugh stage A.

• Cohort 3: Participants must have cholangiocarcinoma.

• Cohort 4: Participants must have chronic lymphocytic leukemia.

• Cohort 5: Participants must have a mature T cell, B cell, or natural killer (NK) cell neoplasm.

• For Part E: Participants must have adenoid cystic carcinoma (ACC).

• For Part F dose confirmation: Participants must have leiomyosarcoma and prescreened alterations in a defined pathway.

• As defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the Revised Response Criteria for Malignant Lymphoma or the Response Assessment in Neuro Oncology (RANO) criteria for glioblastoma:

  • For Dose Escalation (Part A): Have measurable or nonmeasurable disease.
  • For Parts B, C, D, E and F: Have measurable disease or reliable biomarker measure.

• For Parts B, C, D, E and F: Have available tumor tissue.

• Have adequate organ function.

• Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale and life expectancy of more than 12 weeks.

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Exclusion Criteria

• Have symptomatic or non stable central nervous system (CNS) malignancy.

• Females who are pregnant or lactating.

• Have active bacterial, fungal, and/or known viral infection.

• Have malabsorptive syndromes, enteropathies, gastroenteritis (acute or chronic), or diarrhea (acute or chronic).

• Participants with HCC that:

  • Have known HCC with fibro-lamellar or mixed histology.
  • Have presence of clinically relevant ascites.
  • Have had a liver transplant.
  • Have active or uncontrolled clinically serious hepatitis B virus or hepatitis C virus infection.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose 1 LY3039478 + Prednisone	LY3039478	Part F1: LY3039478 administered orally TIW for 28 day cycles. Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression.
Dose 2 LY3039478 + Prednisone	LY3039478	Part F2: LY3039478 administered orally TIW (twice a week in cycle 1) for 28 day cycles. Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only. Participants receiving benefit may continue until disease progression.
LY3039478 - Dose Escalation	LY3039478	Part A: LY3039478 administered orally three times per week (TIW) at escalating doses (2.5 milligrams \[mg\] to 100 mg) for two 28 day cycles. Participants receiving benefit may continue until disease progression
LY3039478 - Cohort Expansion	LY3039478	Part B, C, D and E: LY3039478 administered orally three times per week (TIW) at a fixed dose determined in Part A for two 28 day cycles. Participants receiving benefit may continue until disease progression.
Dose 1 LY3039478 + Prednisone	Prednisone	Part F1: LY3039478 administered orally TIW for 28 day cycles. Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression.
Dose 2 LY3039478 + Prednisone	Prednisone	Part F2: LY3039478 administered orally TIW (twice a week in cycle 1) for 28 day cycles. Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only. Participants receiving benefit may continue until disease progression.

Primary Outcome Measures

Name	Time	Method
Part A and F: Number of Participants with Dose Limiting Toxicities (DLTs)	Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)
Part B, C, D, E and F: Number of Participants with Tumor Response	Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics: Time to Maximum Concentration (Tmax) of LY3039478	Predose up to 30 hours post dose
Pharmacokinetics: Maximum Concentration (Cmax) of LY3039478	Predose up to 30 hours post dose
Part B, C, D, E and F: Duration of Response (DoR)	Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 6 Months)
Part B, C, D, E and F: Progression Free Survival (PFS)	Baseline to Objective Progression or Death from Any Cause (Estimated up to 6 Months)
Part B, C, D, E and F: Overall Survival (OS)	Baseline to Date of Death from Any Cause (Estimated up to 14 Months)
Part A: Number of Participants with Tumor Response	Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)

Trial Locations

Locations (6)

University of Miami School of Medicine; 🇺🇸 Miami, Florida, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

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.; 🇬🇧 London, United Kingdom

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Harvard Medical School; 🇺🇸 Boston, Massachusetts, United States

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States