- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01695005
A Study of LY3039478 in Participants With Advanced Cancer
August 6, 2018 updated by: Eli Lilly and Company
A Phase 1 Study of LY3039478 in Patients With Advanced or Metastatic Cancer
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
237
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Kobenhavn, Denmark, 2100
- 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.
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Paris, France, 75248
- 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.
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Villejuif, France, 94805
- 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.
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Tübingen, Germany, 72076
- 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.
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Barcelona, Spain, 08035
- 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.
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London, United Kingdom, SE1 9RT
- 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.
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Florida
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Miami, Florida, United States, 33136
- University of Miami School of Medicine
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Harvard Medical School
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan
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New York
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Bronx, New York, United States, 10461
- Montefiore Medical Center
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New York, New York, United States, 10032
- Columbia University Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: LY3039478 - Dose Escalation
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
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Administered orally
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Experimental: LY3039478 - Cohort Expansion
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.
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Administered orally
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Experimental: Dose 1 LY3039478 + 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.
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Administered orally
Administered orally
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Experimental: Dose 2 LY3039478 + 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.
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Administered orally
Administered orally
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Part A and F: Number of Participants with Dose Limiting Toxicities (DLTs)
Time Frame: Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)
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Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)
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Part B, C, D, E and F: Number of Participants with Tumor Response
Time Frame: Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)
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Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Pharmacokinetics: Maximum Concentration (Cmax) of LY3039478
Time Frame: Predose up to 30 hours post dose
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Predose up to 30 hours post dose
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Pharmacokinetics: Time to Maximum Concentration (Tmax) of LY3039478
Time Frame: Predose up to 30 hours post dose
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Predose up to 30 hours post dose
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Part A: Number of Participants with Tumor Response
Time Frame: Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)
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Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)
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Part B, C, D, E and F: Duration of Response (DoR)
Time Frame: Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 6 Months)
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Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 6 Months)
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Part B, C, D, E and F: Progression Free Survival (PFS)
Time Frame: Baseline to Objective Progression or Death from Any Cause (Estimated up to 6 Months)
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Baseline to Objective Progression or Death from Any Cause (Estimated up to 6 Months)
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Part B, C, D, E and F: Overall Survival (OS)
Time Frame: Baseline to Date of Death from Any Cause (Estimated up to 14 Months)
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Baseline to Date of Death from Any Cause (Estimated up to 14 Months)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Azaro A, Baldini C, Rodon J, Soria JC, Yuen E, Lithio A, Oakley G, Benhadji KA, Massard C. Phase 1 study of 2 high dose intensity schedules of the pan-Notch inhibitor crenigacestat (LY3039478) in combination with prednisone in patients with advanced or metastatic cancer. Invest New Drugs. 2021 Feb;39(1):193-201. doi: 10.1007/s10637-020-00944-z. Epub 2020 Sep 11.
- Mir O, Azaro A, Merchan J, Chugh R, Trent J, Rodon J, Ohnmacht U, Diener JT, Smith C, Yuen E, Oakley GJ 3rd, Le Cesne A, Soria JC, Benhadji KA, Massard C. Notch pathway inhibition with LY3039478 in soft tissue sarcoma and gastrointestinal stromal tumours. Eur J Cancer. 2018 Nov;103:88-97. doi: 10.1016/j.ejca.2018.08.012. Epub 2018 Sep 12.
- Massard C, Azaro A, Soria JC, Lassen U, Le Tourneau C, Sarker D, Smith C, Ohnmacht U, Oakley G, Patel BKR, Yuen ESM, Benhadji KA, Rodon J. First-in-human study of LY3039478, an oral Notch signaling inhibitor in advanced or metastatic cancer. Ann Oncol. 2018 Sep 1;29(9):1911-1917. doi: 10.1093/annonc/mdy244.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2012
Primary Completion (Actual)
June 26, 2018
Study Completion (Actual)
June 26, 2018
Study Registration Dates
First Submitted
September 24, 2012
First Submitted That Met QC Criteria
September 24, 2012
First Posted (Estimate)
September 27, 2012
Study Record Updates
Last Update Posted (Actual)
August 7, 2018
Last Update Submitted That Met QC Criteria
August 6, 2018
Last Verified
August 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 14547
- I6F-MC-JJCA (Other Identifier: Eli Lilly and Company)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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