A Study of LY2835219 in Japanese Participants With Advanced Cancer

A Phase 1 Study of LY2835219 in Japanese Patients With Advanced Cancer

The main purpose of this study is to evaluate safety and side effects of LY2835219 in Japanese participants with advanced cancer.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Neoplasm Metastasis
• Intervention / Treatment: Drug: LY2835219

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 104-0045
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM to 5 PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have histological or cytological evidence of a diagnosis of cancer (either a solid tumor or a lymphoma) that is advanced and/or metastatic
• 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 non-measurable disease as defined by the Response Evaluation Criteria in Solid Tumors Guideline Version 1.1, or the Revised Response Criteria for Malignant Lymphoma Guideline
• Have adequate organ function
• Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, and investigational therapy, for at least 21 days before the first dose of study drug and recovered from the acute effects of any such therapy
• Males must agree to use medically approved barrier contraceptive precautions during the study and for 3 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 3 months following the last dose of study drug, must have had a negative serum or urine 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 3 months after the last administration
• Have an estimated life expectancy of ≥12 weeks
• Are able to swallow capsules

Exclusion Criteria:

• Have received treatment within 21 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication
• Have a medical history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (e.g., ventricular tachycardia and ventricular fibrillation) or sudden cardiac arrest
• Have a baseline with any of the following findings on screening electrocardiogram (ECG): ventricular tachycardia, ventricular fibrillation, abnormal QTc using Bazett's formula (QTcB) (defined as ≥470 milliseconds), or evidence of acute myocardial ischemia
• Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, history of major surgical resection involving the stomach or small bowel)
• Have symptomatic central nervous system (CNS) malignancy or metastasis. For asymptomatic participants without history of CNS malignancy or metastases
• Have evidence or history of a leukemia
• Have received a stem-cell transplant. As an exception, a participant with lymphoma who received an autologous stem-cell transplant is eligible for the study, if more than 75 days have passed before the initial dose of study drug
• Have active bacterial, fungal, and/or known viral infection (for example, human immunodeficiency virus [HIV], hepatitis B, or hepatitis C)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 - 100 mg Abemaciclib; 100 milligram (mg) abemaciclib administered orally every 12 hours (Q12H) in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Drug: LY2835219; Administered orally; Other Names: abemaciclib
Experimental: Cohort 2 - 150 mg Abemaciclib; 150 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Drug: LY2835219; Administered orally; Other Names: abemaciclib
Experimental: Cohort 3 - 200 mg Abemaciclib; 200 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met.	Drug: LY2835219; Administered orally; Other Names: abemaciclib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Abemaciclib Dose-Limiting Toxicity (DLT)	DLT is defined as an adverse event between Day -3 and Day 29 of Cycle 1 that is possibly related to the study drug and fulfills any one of the following criteria using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.	Cycle 1 = 32 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Abemaciclib	Maximum plasma concentration on Day -3 and Day 28 of Cycle 1.	Cycle 1 Day -3: Predose, 1, 2, 4, 6, 8, 10, 24, 48 and 72 hours (hr) postdose; Cycle 1 Day 28: Predose, 1, 2, 4, 6, 8, 10 and 24 hr postdose (Cycle 1 = 32 days)
Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of Abemaciclib	AUC on Day -3 and Day 28 of Cycle 1 are AUC from time zero to infinity [AUC(0-∞)] and AUC during one dosing interval at steady state (AUCτ,ss), respectively.	Cycle 1 Day -3: Predose, 1, 2, 4, 6, 8, 10, 24, 48 and 72 hr postdose; Cycle 1 Day 28: Predose, 1, 2, 4, 6, 8, 10 and 24 hr postdose (Cycle 1 = 32 days)
Percentage of Participants With a Tumor Response: Objective Response Rate (ORR)	Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as having at least a 30% decrease in sum of longest diameter of target lesions.	Baseline to Measured Progressive Disease (Up To 24 months)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Gelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, Torres R, Ajamie RT, Wishart GN, Flack RS, Neubauer BL, Young J, Chan EM, Iversen P, Cronier D, Kreklau E, de Dios A. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 2014 Oct;32(5):825-37. doi: 10.1007/s10637-014-0120-7. Epub 2014 Jun 13.

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2013
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): August 21, 2019

Study Registration Dates

• First Submitted: December 12, 2013
• First Submitted That Met QC Criteria: December 12, 2013
• First Posted (Estimate): December 18, 2013

Study Record Updates

• Last Update Posted (Actual): August 24, 2020
• Last Update Submitted That Met QC Criteria: August 7, 2020
• Last Verified: September 15, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: 15154; I3Y-JE-JPBC (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO