A Study of LY2940680 in Japanese Participants With Advanced Cancers

Neoplasm Metastasis Clinical Trial

Official title:

A Phase 1 Study of LY2940680 in Japanese Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01919398
• Other study ID #: 14895 TRANSFERRED
• Secondary ID: I4J-MC-HHBH
• Status: Completed
• Phase: Phase 1
• Start date: August 2013
• Est. completion date: June 28, 2017

Study information

• Verified date: August 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: June 28, 2017
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasm Metastasis

Intervention

Drug:
• LY2940680
Administered orally

Locations

Country	Name	City	State
Japan	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.	Shizuoka
Japan	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.	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 .	Cycle 1 (28 Days)
Secondary	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).	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
Secondary	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.	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
Secondary	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.	Baseline Until Disease Progression or Death Due to Any Cause (Up to 29 Months)
Secondary	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.	Baseline, Cycle 1 Day15