A Study of Abemaciclib (LY2835219) in Native Chinese Participants With Advanced and/or Metastatic Cancers

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the safety of the study drug known as abemaciclib in native Chinese participants with advanced and/or metastatic cancers.

Official Title
-----------------
A Phase 1 Study of Abemaciclib in Native Chinese Patients With Advanced and/or Metastatic Cancers

Conditions
-----------------
Advanced Cancer, Metastatic Cancer

Intervention / Treatment
-----------------
* Drug: Abemaciclib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The participant must have histological or cytological evidence of cancer which is advanced and/or metastatic, and is an appropriate candidate for experimental therapy in the judgment of the investigator, after available standard therapies have ceased to provide clinical benefit. Have the presence of measureable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Are native Chinese men or women. Have adequate organ function, including: Hematologic: Absolute neutrophil count (ANC) ≥1.5 x 109/Liters (L), platelets ≥100 x 109/L, and hemoglobin ≥9 grams per deciliter. Participants may receive erythrocyte transfusions to achieve this hemoglobin level or platelet transfusions to achieve platelet levels at the discretion of the investigator; however, initial study drug treatment must not begin earlier than the day after transfusion. Hepatic: Bilirubin ≤1.5 times upper limits of normal (ULN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3.0 times ULN. Renal: Serum creatinine ≤1.2 milligrams per deciliter (mg/dL) for males or ≤1.0 mg/dL for females. Have a performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale. Recovered from the acute effects of therapy (treatment- related toxicity resolved to baseline) except for residual alopecia. Have an estimated life expectancy of ≥12 weeks. Exclusion Criteria: Have received previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy) within 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug. Have an acute leukemia or other relevant cancers at the discretion of the investigator. Females who are pregnant or lactating. Participants consuming drugs or foods that are known to be inducers (for example, grapefruit juice, phenytoin, carbamazepine) or strong inhibitors of CYP3A4 should be excluded during Cycle 1. Have history or evidence of central nervous system (CNS) malignancy or metastasis. Screening of asymptomatic participants without history of CNS metastases is not required for enrollment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abemaciclib Dose Level 1<br>Abemaciclib 150 milligram (mg) administered every 12 hours, orally, cycle 1 and then in cycle 2. Participants may continue to receive treatment until discontinuation criteria are met. One cycle is defined as 28 days. (Cycle 1: 32 days), with modifications during Cycle 1 to enable pharmacokinetic (PK) sampling following a single dose and repeated doses. | Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;|
| Experimental: Abemaciclib Dose Level 2<br>Abemaciclib 200 mg administered every 12 hours, orally, cycle 1 and then in cycle 2. Participants may continue to receive treatment until discontinuation criteria are met. One cycle is defined as 28 days. (Cycle 1: 32 days), with modifications during Cycle 1 to enable PK sampling following a single dose and repeated doses. | Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With One or More Drug Related Adverse Events | Number of participants with one or more drug related adverse events. Clinically significant events were defined as serious adverse events, regardless of causality. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module. | Baseline through End of Study (Up to 10 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib and Its Metabolites Single Dose | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib and its Metabolites following a single oral dose. | Cycle 1, Day(D)1; Predose, 1, 4, 6, 8, 10, 24, 48 Hours Postdose | 
| PK: Maximum Concentration (Cmax) of Abemaciclib and Its Metabolites (Twice Daily Dosing) | PK: Maximum Concentration (Cmax) of Abemaciclib and its Metabolites following a twice daily dosing. | Cycle 1, Day(D) 31; Predose, 1, 2, 4, 6, 8, 10, 24 Hours Postdose | 
| PK: Area Under Concentration Time Curve (AUC) From Time Zero to 12 Hours (AUC [0-12]) of Abemaciclib and Its Metabolites Single Dose | PK: Area Under Concentration Time Curve (AUC) from Time Zero to 12 hours (AUC [0-12]) of Abemaciclib and its Metabolites following a single oral dose. | Cycle 1, Day(D)1; Predose, 1, 4, 6, 8, 10, 24, 48 Hours Postdose | 
| PK: AUC From Time Zero to 12 Hours (AUC [0-12]) of Abemaciclib and Its Metabolites (Twice Daily Dosing) | PK: AUC from Time Zero to 12 hours (AUC [0-12]) of Abemaciclib and its Metabolites following twice daily dosing | Cycle 1, Day(D) 31; Predose, 1, 2, 4, 6, 8, 10, 24 Hours Postdose | 
| PK: AUC From Time Zero to Infinity (AUC[0-inf]) of Abemaciclib and Its Metabolites Single Dose | PK: AUC from Time Zero to Infinity (AUC[0-inf]) of Abemaciclib and its Metabolites following a single oral dose. | Cycle 1, Day(D)1; Predose, 1, 4, 6, 8, 10, 24, 48 Hours Postdose | 
| Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | ORR was defined as the percentage of randomized participants with a best overall response of complete response (CR) or partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. Participants with unevaluable or unknown response status are considered nonresponders. Complete response (CR) is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. Partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions and no appearance of new lesions. Progressive disease (PD) is defined as at least a 20% increase in the sum LD of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) and the 20% increase must be at least one lesion must increase by an absolute value of ≥5 mm to be considered progression. | Baseline to Measured Progressive Disease (Up to 13 Months ) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CDK4/6 Inhibitor