A Study of LY2940680 in Japanese Participants With Advanced Cancers

NCT01919398 | Completed Phase 1 Results

• 2 other identifiers: 14895 TRANSFERREDI4J-MC-HHBH
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

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.

Conditions

Neoplasm Metastasis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

• 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

• 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)

• Pharmacodynamic (PD): Percentage Change From Baseline in Gene Expression Level of Hedgehog (Hh) Regulated Genes (Gli1) in Skin

  Baseline, Cycle 1 Day15

Study Arms (1)

LY2940680

EXPERIMENTAL

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.

Drug: LY2940680

Interventions

LY2940680 DRUG

Administered orally

LY2940680

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (2)

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, 411-8777, Japan

Location

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, 104-0045, Japan

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

LY2940680

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 1-858-255-5959 Mon-Fri from 9 AM to 5 PM Pacific Time (PST)

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2013
• First Posted: August 9, 2013
• Study Start: August 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: June 28, 2017
• Last Updated: September 11, 2019
• Results First Posted: September 11, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

JP (2)