Back to resultsA Study of LY2940680 in Japanese Participants With Advanced Cancers
Primary Purpose
Neoplasm Metastasis
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
LY2940680
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasm Metastasis
Eligibility Criteria
Inclusion Criteria:
- Have histological or cytological evidence of a diagnosis of solid tumor that is advanced and/or metastatic. The participant must be, in the judgment of the investigator, an appropriate candidate for the experimental therapy after available standard therapies have failed to provide clinical benefit for their disease
- Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors Guideline Version 1.1
- Have adequate organ function
- Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy for at least 3 weeks (6 weeks for mitomycin-C or nitrosoureas, 2 weeks for palliative radiation therapy for bone metastasis) prior to study enrollment, and have recovered from the acute effects of any such therapy
- Males must agree to use medically approved barrier contraceptive precautions during the study and for 6 months following the last dose of study drug
- Females with child bearing potential must agree to use medically approved contraceptive precautions during the study and for 6 months following the last dose of study drug; have had a negative serum pregnancy test ≤7 days before the first dose of study drug
- A breastfeeding woman must not be breastfeeding. If a female who stops breastfeeding enters the study, the female must stop breastfeeding from the day of the first study drug administration until at least 6 months after the last administration
- Have an estimated life expectancy, in the judgment of the investigator, which will permit the participant to complete 2 cycles of treatment
- Are able to swallow tablets
Exclusion Criteria:
- Have received treatment within 21 days of the study enrollment with any agent that has not received regulatory approval for any indication
- Have symptomatic central nervous system (CNS) malignancy or metastasis. Participants with treated brain metastases are eligible if they are clinically stable with regard to neurologic function and off steroids after cranial irradiation ending at least 14 days prior to enrollment, or after surgical resection performed at least 28 days prior to enrollment
- Have known current hematologic malignancies or acute or chronic leukemia
- Have a known active fungal, bacterial, and/or known viral infection including human immunodeficiency (HIV) or viral (A, B, or C) hepatitis, potentially affecting the conduct of this study
- Have a second primary malignancy that in the judgment of the investigator and sponsor may affect the interpretation of results
- Have QTc interval of >470 milliseconds (msec) on screening electrocardiogram (ECG)
- Have serious preexisting medical conditions or serious concomitant systemic disorders that, in the opinion of the investigator, would preclude participation in this study
- Have received any medication that is a strong inhibitor of cytochrome P4503A4 (CYP3A4) within 7 days prior to receiving study drug
Sites / Locations
- For additional information regarding investigative sites for this trial, contact 1-858-255-5959 Mon - Fri from 9 AM to 5 PM Pacific Time (PST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-858-255-5959 Mon - Fri from 9 AM to 5 PM Pacific Time (PST), or speak with your personal physician.
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
LY2940680
Arm Description
Cohort 1: 100 mg LY2940680 administered orally daily in 28-day cycles. Cohort 2: 200 mg LY2940680 administered orally daily in 28-day cycles. Cohort 3: 400 mg LY2940680 administered orally daily in 28-day cycles. Treatment with LY2940680 continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met.
Outcomes
Primary Outcome Measures
Number of Participants With LY2940680 Dose-Limiting Toxicities (DLT)
DLT was defined as an AE during Cycle 1 that is possibly related to the study drug and meets any one of the following criteria based on NCI CTCAE,version 4.0): Grade(Gr) 3 nonhematological toxicity(tox) with exceptions for made for nausea(ns),vomiting(vm),constipation(cp),diarrhea(dr),fatigue(ft),anorexia(an),alopecia or electrolyte-abnormality(eab) that is manageable with appropriate care.If >Gr 3 ns,vm,cp,dr,ft,an,or eab persists for>2 days with maximal supportive intervention,the event was declared a DLT.Transient(≤5 days) Gr 3 liver enzyme elevations,without evidence of other hepatic injury.Gr 3 thrombocytopenia(throm) requiring platelet transfusion or Gr 4 throm.Gr 4 neutropenia of >5 days duration.Febrile neutropenia(ANC<1,000/mm3 with a single temperature(temp) of >38.3 degrees C or a sustained temp of ≥38 degrees C for more than one hour).Tox requiring dose omissions of >5 days or significant & deemed by the primary investigator(PI) & sponsor(sp) to be dose limiting .
Secondary Outcome Measures
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680 and a Major Metabolite of LY2940680 (LSN3185556)
Maximum Concentration (Cmax) of LY2940680 and a Major Metabolite of LY2940680 (LSN3185556).
Pharmacokinetics (PK): Area Under the Concentration Time Curve From 0 to 24 Hours (AUC[0-24]) of LY2940680 and a Major Metabolite of LSN3185556
Pharmacokinetics (PK): Area Under the Concentration time Curve From 0 to 24 Hours (AUC[0-24]) of LY2940680 and a Major Metabolite of LSN3185556.
Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR])
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and all target and non-target lymph nodes were non-pathological or normal in size (<10 millimeter [mm] short axis). PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions taking as reference the baseline sum diameters. ORR calculated as: (sum of the number of participants with PRs and CRs) divided by (number of evaluable participants) multiplied by 100.
Pharmacodynamic (PD): Percentage Change From Baseline in Gene Expression Level of Hedgehog (Hh) Regulated Genes (Gli1) in Skin
Percentage Change From Baseline in Gene Expression Level of Hedgehog (Hh) Regulated Genes (Gli1) in Skin.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01919398
Brief Title
A Study of LY2940680 in Japanese Participants With Advanced Cancers
Official Title
A Phase 1 Study of LY2940680 in Japanese Patients With Advanced Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
August 2013 (undefined)
Primary Completion Date
May 2016 (Actual)
Study Completion Date
June 28, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary purpose of this study is to assess the safety and tolerability of LY2940680 up to the global recommended dose in Japanese participants with advanced solid cancers.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasm Metastasis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LY2940680
Arm Type
Experimental
Arm Description
Cohort 1: 100 mg LY2940680 administered orally daily in 28-day cycles. Cohort 2: 200 mg LY2940680 administered orally daily in 28-day cycles. Cohort 3: 400 mg LY2940680 administered orally daily in 28-day cycles.
Treatment with LY2940680 continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met.
Intervention Type
Drug
Intervention Name(s)
LY2940680
Intervention Description
Administered orally
Primary Outcome Measure Information:
Title
Number of Participants With LY2940680 Dose-Limiting Toxicities (DLT)
Description
DLT was defined as an AE during Cycle 1 that is possibly related to the study drug and meets any one of the following criteria based on NCI CTCAE,version 4.0): Grade(Gr) 3 nonhematological toxicity(tox) with exceptions for made for nausea(ns),vomiting(vm),constipation(cp),diarrhea(dr),fatigue(ft),anorexia(an),alopecia or electrolyte-abnormality(eab) that is manageable with appropriate care.If >Gr 3 ns,vm,cp,dr,ft,an,or eab persists for>2 days with maximal supportive intervention,the event was declared a DLT.Transient(≤5 days) Gr 3 liver enzyme elevations,without evidence of other hepatic injury.Gr 3 thrombocytopenia(throm) requiring platelet transfusion or Gr 4 throm.Gr 4 neutropenia of >5 days duration.Febrile neutropenia(ANC<1,000/mm3 with a single temperature(temp) of >38.3 degrees C or a sustained temp of ≥38 degrees C for more than one hour).Tox requiring dose omissions of >5 days or significant & deemed by the primary investigator(PI) & sponsor(sp) to be dose limiting .
Time Frame
Cycle 1 (28 Days)
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680 and a Major Metabolite of LY2940680 (LSN3185556)
Description
Maximum Concentration (Cmax) of LY2940680 and a Major Metabolite of LY2940680 (LSN3185556).
Time Frame
Cycle1 Day1: Predose, 0.5,1,2,4, 6, 8, 10-12 hours; Cycle 1 Day15: Predose, 0.5,1,2,4, 6, 8, 10-12 hours
Title
Pharmacokinetics (PK): Area Under the Concentration Time Curve From 0 to 24 Hours (AUC[0-24]) of LY2940680 and a Major Metabolite of LSN3185556
Description
Pharmacokinetics (PK): Area Under the Concentration time Curve From 0 to 24 Hours (AUC[0-24]) of LY2940680 and a Major Metabolite of LSN3185556.
Time Frame
Cycle1 Day1: Predose, 0.5,1,2,4, 6, 8, 10-12 hours; Cycle 1 Day15: Predose, 0.5,1,2,4, 6, 8, 10-12 hours
Title
Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR])
Description
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and all target and non-target lymph nodes were non-pathological or normal in size (<10 millimeter [mm] short axis). PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions taking as reference the baseline sum diameters. ORR calculated as: (sum of the number of participants with PRs and CRs) divided by (number of evaluable participants) multiplied by 100.
Time Frame
Baseline Until Disease Progression or Death Due to Any Cause (Up to 29 Months)
Title
Pharmacodynamic (PD): Percentage Change From Baseline in Gene Expression Level of Hedgehog (Hh) Regulated Genes (Gli1) in Skin
Description
Percentage Change From Baseline in Gene Expression Level of Hedgehog (Hh) Regulated Genes (Gli1) in Skin.
Time Frame
Baseline, Cycle 1 Day15
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have histological or cytological evidence of a diagnosis of solid tumor that is advanced and/or metastatic. The participant must be, in the judgment of the investigator, an appropriate candidate for the experimental therapy after available standard therapies have failed to provide clinical benefit for their disease
Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors Guideline Version 1.1
Have adequate organ function
Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy for at least 3 weeks (6 weeks for mitomycin-C or nitrosoureas, 2 weeks for palliative radiation therapy for bone metastasis) prior to study enrollment, and have recovered from the acute effects of any such therapy
Males must agree to use medically approved barrier contraceptive precautions during the study and for 6 months following the last dose of study drug
Females with child bearing potential must agree to use medically approved contraceptive precautions during the study and for 6 months following the last dose of study drug; have had a negative serum pregnancy test ≤7 days before the first dose of study drug
A breastfeeding woman must not be breastfeeding. If a female who stops breastfeeding enters the study, the female must stop breastfeeding from the day of the first study drug administration until at least 6 months after the last administration
Have an estimated life expectancy, in the judgment of the investigator, which will permit the participant to complete 2 cycles of treatment
Are able to swallow tablets
Exclusion Criteria:
Have received treatment within 21 days of the study enrollment with any agent that has not received regulatory approval for any indication
Have symptomatic central nervous system (CNS) malignancy or metastasis. Participants with treated brain metastases are eligible if they are clinically stable with regard to neurologic function and off steroids after cranial irradiation ending at least 14 days prior to enrollment, or after surgical resection performed at least 28 days prior to enrollment
Have known current hematologic malignancies or acute or chronic leukemia
Have a known active fungal, bacterial, and/or known viral infection including human immunodeficiency (HIV) or viral (A, B, or C) hepatitis, potentially affecting the conduct of this study
Have a second primary malignancy that in the judgment of the investigator and sponsor may affect the interpretation of results
Have QTc interval of >470 milliseconds (msec) on screening electrocardiogram (ECG)
Have serious preexisting medical conditions or serious concomitant systemic disorders that, in the opinion of the investigator, would preclude participation in this study
Have received any medication that is a strong inhibitor of cytochrome P4503A4 (CYP3A4) within 7 days prior to receiving study drug
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
1-858-255-5959 Mon-Fri from 9 AM to 5 PM Pacific Time (PST)
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
For additional information regarding investigative sites for this trial, contact 1-858-255-5959 Mon - Fri from 9 AM to 5 PM Pacific Time (PST), or speak with your personal physician.
City
Shizuoka
ZIP/Postal Code
411-8777
Country
Japan
Facility Name
For additional information regarding investigative sites for this trial, contact 1-858-255-5959 Mon - Fri from 9 AM to 5 PM Pacific Time (PST), or speak with your personal physician.
City
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of LY2940680 in Japanese Participants With Advanced Cancers
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