A Study of LY2940680 in Japanese Participants With Advanced Cancers

Phase 1

Completed

• Conditions: Neoplasm Metastasis
• Interventions: Drug: LY2940680

• Registration Number: NCT01919398
• Lead Sponsor: Eli Lilly and Company

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-08
• Study First Submitted: 2013-08-05
• Study First Submitted QC: 2013-08-07
• Study First Posted: 2013-08-09
• Primary Completion: 2016-05
• Study Completion: 2017-06-28
• Results First Submitted: 2019-05-08
• Status Verified: 2019-08
• Results First Submitted QC: 2019-08-01
• Last Update Submitted: 2019-08-01
• Results First Posted: 2019-09-11
• Last Update Posted: 2019-09-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LY2940680	LY2940680	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With LY2940680 Dose-Limiting Toxicities (DLT)	Cycle 1 (28 Days)	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

Name	Time	Method
Pharmacokinetics (PK): 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	Maximum Concentration (Cmax) of LY2940680 and a Major Metabolite of LY2940680 (LSN3185556).
Pharmacodynamic (PD): Percentage Change From Baseline in Gene Expression Level of Hedgehog (Hh) Regulated Genes (Gli1) in Skin	Baseline, Cycle 1 Day15	Percentage Change From Baseline in Gene Expression Level of Hedgehog (Hh) Regulated Genes (Gli1) in Skin.
Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR])	Baseline Until Disease Progression or Death Due to Any Cause (Up to 29 Months)	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.
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	Pharmacokinetics (PK): Area Under the Concentration time Curve From 0 to 24 Hours (AUC\[0-24\]) of LY2940680 and a Major Metabolite of LSN3185556.

Trial Locations

Locations (1)

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, Japan