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

• ClinicalTrials.gov Identifier: NCT02919696
• Recruitment Status: Completed
• First Posted: September 29, 2016
• Results First Posted: September 25, 2020
• Last Update Posted: September 25, 2020
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Cancer; Metastatic Cancer	Drug: Abemaciclib	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of Abemaciclib in Native Chinese Patients With Advanced and/or Metastatic Cancers
• Actual Study Start Date: August 7, 2017
• Actual Primary Completion Date: November 23, 2018
• Actual Study Completion Date: September 3, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Abemaciclib Dose Level 1; 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; Administered orally; Other Name: LY2835219
Experimental: Abemaciclib Dose Level 2; 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; Administered orally; Other Name: LY2835219

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With One or More Drug Related Adverse Events [ Time Frame: Baseline through End of Study (Up to 10 Months) ]
   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.

Secondary Outcome Measures :

1. Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib and Its Metabolites Single Dose [ Time Frame: Cycle 1, Day(D)1; Predose, 1, 4, 6, 8, 10, 24, 48 Hours Postdose ]
   Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib and its Metabolites following a single oral dose.
2. PK: Maximum Concentration (Cmax) of Abemaciclib and Its Metabolites (Twice Daily Dosing) [ Time Frame: Cycle 1, Day(D) 31; Predose, 1, 2, 4, 6, 8, 10, 24 Hours Postdose ]
   PK: Maximum Concentration (Cmax) of Abemaciclib and its Metabolites following a twice daily dosing.
3. PK: Area Under Concentration Time Curve (AUC) From Time Zero to 12 Hours (AUC [0-12]) of Abemaciclib and Its Metabolites Single Dose [ Time Frame: Cycle 1, Day(D)1; Predose, 1, 4, 6, 8, 10, 24, 48 Hours Postdose ]
   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.
4. PK: AUC From Time Zero to 12 Hours (AUC [0-12]) of Abemaciclib and Its Metabolites (Twice Daily Dosing) [ Time Frame: Cycle 1, Day(D) 31; Predose, 1, 2, 4, 6, 8, 10, 24 Hours Postdose ]
   PK: AUC from Time Zero to 12 hours (AUC [0-12]) of Abemaciclib and its Metabolites following twice daily dosing
5. PK: AUC From Time Zero to Infinity (AUC[0-inf]) of Abemaciclib and Its Metabolites Single Dose [ Time Frame: Cycle 1, Day(D)1; Predose, 1, 4, 6, 8, 10, 24, 48 Hours Postdose ]
   PK: AUC from Time Zero to Infinity (AUC[0-inf]) of Abemaciclib and its Metabolites following a single oral dose.
6. Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline to Measured Progressive Disease (Up to 13 Months ) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

China

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.

Changsha, China, 410013

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.

Shanghai, China, 200030

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.

Shanghai, China

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:

Statistical Analysis Plan  [PDF] December 13, 2018

Study Protocol  [PDF] April 12, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Zhang J, Yang N, Ji D, Shen W, Li W, Han R, Wang N, Tao H, Chapman SC, Sykes AK, Zhang W, Hu X. A Randomized Phase I Study of Abemaciclib in Chinese Patients with Advanced and/or Metastatic Cancers. Target Oncol. 2021 Mar;16(2):177-187. doi: 10.1007/s11523-020-00789-9. Epub 2021 Jan 25.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02919696
• Other Study ID Numbers: 15531; I3Y-CR-JPBR ( Other Identifier: Eli Lilly and Company )
• First Posted: September 29, 2016
• Results First Posted: September 25, 2020
• Last Update Posted: September 25, 2020
• Last Verified: December 1, 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eli Lilly and Company:

CDK4/6 Inhibitor

Additional relevant MeSH terms:

Neoplasm Metastasis; Neoplasms; Neoplasms, Second Primary; Neoplastic Processes; Pathologic Processes