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.
Brief Title
A Study of LY3039478 in Participants With Advanced Cancer
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Neoplasms
Neoplasm Metastasis
Lymphoma
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01695005
Org Class
Industry
Org Full Name
Eli Lilly and Company
Org Study Id
14547
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 1 Study of LY3039478 in Patients With Advanced or Metastatic Cancer
Primary Outcomes
Outcome Measure
Part A and F: Number of Participants with Dose Limiting Toxicities (DLTs)
Outcome Time Frame
Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)
Outcome Measure
Part B, C, D, E and F: Number of Participants with Tumor Response
Outcome Time Frame
Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)
Secondary Ids
Secondary Id
I6F-MC-JJCA
Secondary Outcomes
Outcome Time Frame
Predose up to 30 hours post dose
Outcome Measure
Pharmacokinetics: Maximum Concentration (Cmax) of LY3039478
Outcome Time Frame
Predose up to 30 hours post dose
Outcome Measure
Pharmacokinetics: Time to Maximum Concentration (Tmax) of LY3039478
Outcome Time Frame
Baseline to disease progression or participant discontinuation (estimated 8 -12 weeks)
Outcome Measure
Part A: Number of Participants with Tumor Response
Outcome 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)
Outcome Measure
Part B, C, D, E and F: Duration of Response (DoR)
Outcome Time Frame
Baseline to Objective Progression or Death from Any Cause (Estimated up to 6 Months)
Outcome Measure
Part B, C, D, E and F: Progression Free Survival (PFS)
Outcome Time Frame
Baseline to Date of Death from Any Cause (Estimated up to 14 Months)
Outcome Measure
Part B, C, D, E and F: Overall Survival (OS)
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sanjay Goel
Investigator Email
sgoel@montefiore.org
Investigator Phone
718-405-8404
Categories Mesh Debug
Cancer --- NEOPLASMS
Blood & Bone Marrow Cancers --- LYMPHOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- LYMPHATIC DISEASES
Blood & Bone Marrow Cancers --- IMMUNOPROLIFERATIVE DISORDERS
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
MeSH Terms
NEOPLASMS
NEOPLASM METASTASIS
LYMPHOMA
NEOPLASTIC PROCESSES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
NEOPLASMS BY HISTOLOGIC TYPE
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
HEMIC AND LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
IMMUNE SYSTEM DISEASES
CRENIGACESTAT
PREDNISONE
PREGNADIENEDIOLS
PREGNADIENES
PREGNANES
STEROIDS
FUSED-RING COMPOUNDS
POLYCYCLIC COMPOUNDS