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
Estimated
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 Description
DLT was defined as an adverse event (AE) during Cycle 1 (Up to 28 Days) that was related to LY3039478 and fulfilled any 1 of the following criterion using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE v 4.0): CTCAE Grade 3 non-hematological toxicity with a few exceptions, CTCAE Grade 4 hematological toxicity of greater than 5 days duration, any febrile neutropenia,Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia, Any other significant toxicity deemed by the primary investigator and Lilly clinical research personnel to be dose limiting (for example, any toxicity that is possibly related to the study medication that requires the withdrawal of the participant from the study during Cycle 1).
Outcome Measure
Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)
Outcome Time Frame
Baseline through the end of Cycle 1, Up to 28 Days
Outcome Description
MTD is defined as the highest tested dose that has less than 33% probability of causing a DLT during Cycle 1.
Outcome Measure
Part A: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)
Outcome Time Frame
Baseline though the end of cycle 1 (28 days cycle)
Outcome Description
MTD is defined as the highest tested dose that has less than 33% probability of causing a DLT during Cycle 1.
Outcome Measure
Part B, C, D and E: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)
Outcome Time Frame
Baseline through the end of cycle 1 (28 days Cycle)
Outcome Description
Parts F1 and F2 compared loading dose three time per week with prednisone versus two times per week with prednisone. Even though the trial may have found an MTD, it did not identify an Recommended Phase 2 dose (RP2D).
Outcome Measure
Part F1 and F2: Recommended Phase 2 Dose of LY3039478
Outcome Time Frame
Baseline Up to 2 Months
Outcome Description
Objective response is complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST 1.1 ) guidelines. CR is disappearance of all target and non-target lesions; PR is greater than or equal to (\>=) 30% decrease in sum of longest diameter of target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.
Analysis Population Description: Part D: 50 mg LY3039478 (Cohort 5) was assessed using Cheson criteria. Zero participants were analyzed for Part D: 50 mg LY3039478 (Cohort 4) because data were not collected. Data was not reported because both enrolled participants discontinued treatment early-one on Day 1 due to investigator decision and the other on Day 26 due to myocardial infarction, with no efficacy assessments performed.
Analysis Population Description: Part D: 50 mg LY3039478 (Cohort 5) was assessed using Cheson criteria. Zero participants were analyzed for Part D: 50 mg LY3039478 (Cohort 4) because data were not collected. Data was not reported because both enrolled participants discontinued treatment early-one on Day 1 due to investigator decision and the other on Day 26 due to myocardial infarction, with no efficacy assessments performed.
Outcome Measure
Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Outcome Time Frame
Baseline to Disease Progression or Participant Discontinuation (Up To 20 Months)
Secondary Ids
Secondary Id
I6F-MC-JJCA
Secondary Outcomes
Outcome Description
Parts A and B: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478
Analysis Population Description: Per Protocol, only sparse samples were analyzed for this outcome measure. There were no Sparse Day 22 samples for Part B: 50 mg \& 75 mg LY3039478, Part C: 50 mg \&75 LY3039478, Part D: 50 mg \& 75 LY3039478 and Part E: 50 mg LY3039478
Analysis Population Description: Per Protocol, only sparse samples were analyzed for this outcome measure. There were no Sparse Day 22 samples for Part B: 50 mg \& 75 mg LY3039478, Part C: 50 mg \&75 LY3039478, Part D: 50 mg \& 75 LY3039478 and Part E: 50 mg LY3039478
Outcome Time Frame
Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose, 0.5,1,2,4,6-8,8-10,24-30 hours
Outcome Measure
Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478
Outcome Description
Part F1 Cohort 1 and Part F2 and Cohort 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478
Outcome Time Frame
Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose, 0.5,1,2,4,6-8,8-10,24-30 hours
Outcome Measure
Part F1 Cohort1 and Part F2 Cohort 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478
Outcome Description
PK: Area Under the Concentration-Time Curve From time 0 to Infinity (AUC\[0-∞\]) of LY3039478
Analysis Population Description: One participant assigned to the Part A: 45 mg group LY3039478 arm received 75 mg in error on Day 1 and had evaluable PK data. Therefore, this participant is included in the Part A: 75 mg LY3039478 arm PK analysis population (N=6), though only N=5 is shown in the Participant Flow module.
Analysis Population Description: One participant assigned to the Part A: 45 mg group LY3039478 arm received 75 mg in error on Day 1 and had evaluable PK data. Therefore, this participant is included in the Part A: 75 mg LY3039478 arm PK analysis population (N=6), though only N=5 is shown in the Participant Flow module.
Outcome Time Frame
Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Outcome Measure
Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478
Outcome Description
Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From time 0 to Infinity (AUC\[0-∞\]) of LY3039478
Outcome Time Frame
Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Outcome Measure
Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478
Outcome Description
PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC\[0-Tau\]) of LY3039478
Analysis Population Description: Per protocol, AUC0-tau was not analyzed for participants undergoing sparse PK sampling. Part B 50mg participants only underwent sparse PK sampling.
Analysis Population Description: Per protocol, AUC0-tau was not analyzed for participants undergoing sparse PK sampling. Part B 50mg participants only underwent sparse PK sampling.
Outcome Time Frame
Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Outcome Measure
Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478
Outcome Description
PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC\[0-Tau\]) of LY3039478
Outcome Time Frame
Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Outcome Measure
Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478
Outcome Description
Pharmacokinetics: Time to Maximum Concentration (Tmax) of LY3039478
Analysis Population Description: Per Protocol, only sparse samples were analyzed for this outcome measure. There were no Sparse Day 22 samples for Part B: 50 mg \& 75 mg LY3039478, Part C: 50 mg \&75 LY3039478, Part D: 50 mg \& 75 LY3039478 and Part E: 50 mg LY3039478.
Analysis Population Description: Per Protocol, only sparse samples were analyzed for this outcome measure. There were no Sparse Day 22 samples for Part B: 50 mg \& 75 mg LY3039478, Part C: 50 mg \&75 LY3039478, Part D: 50 mg \& 75 LY3039478 and Part E: 50 mg LY3039478.
Outcome Time Frame
Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Outcome Measure
Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478
Outcome Description
Part F1 Cohort1 and Part F2 Cohort 1: PK: Time to Maximum Concentration (Tmax) of LY3039478
Outcome Time Frame
Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Outcome Measure
Part F1 Cohort1 and Part F2 Cohort 1: PK: Time to Maximum Concentration (Tmax) of LY3039478
Outcome Description
Objective response is complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST 1.1 ) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.
Outcome Time Frame
Baseline to Disease Progression or Participant Discontinuation (Up To 17 Months)
Outcome Measure
Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Outcome Description
The time from the date of first evidence of a confirmed complete to the date of objective progression or the date of death from any cause (whichever is earlier) as classified by RECIST 1.1 guidelines. For each participant who is not known to have died or to have had a progression of disease as of the data-inclusion cut-off date, duration of response will be censored at the date of last objective response assessment prior to the date of any subsequent systemic anticancer therapy. Progressive Disease (PD) is an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if that was the smallest on study). In addition, the sum must have demonstrated an absolute increase of at least 5 mm (the appearance of 1 or more new lesions was considered progression).
Outcome Time Frame
Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death Due to Any Cause (Up To 20 Months)
Outcome Measure
Part B, C, D, E and F: Duration of Response (DoR)
Outcome Description
Progression-free survival(PFS) time is defined as the time from the date of study enrollment to the first date of PD(symptomatic or objective) or death due to any cause,whichever occurs first.For participants who are not known to have died or progressed as of the data-inclusion cut-off date,PFS time will be censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systemic anticancer therapy. Progressive Disease(PD) is an increase of at least 20% in the sum of the diameters of target lesions,taking as reference the smallest sum on study(included baseline sum if that was the smallest on study).In addition, the sum must have demonstrated an absolute increase of at least 5 mm(the appearance of 1 or more new lesions was considered progression).
Analysis Population Description Continued:Part D:50 mg LY3039478(Cohort 4) and Part D:50 mg LY3039478(Cohort 5) were not assessed according to RECIST criteria due to their type of disease.
Analysis Population Description Continued:Part D:50 mg LY3039478(Cohort 4) and Part D:50 mg LY3039478(Cohort 5) were not assessed according to RECIST criteria due to their type of disease.
Outcome Time Frame
Baseline to Objective Progression or Death from Any Cause (Up To 17 Months)
Outcome Measure
Part B, C, D, E and F: Progression Free Survival (PFS)
Outcome Description
Overall Survival (OS) was defined as the time from the date of study enrollment to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participants was known to be alive prior to the cut-off date.
Outcome Time Frame
Baseline to Date of Death from Any Cause (Up To 49 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