A Phase 1 Study of LY2835219 In Participants With Advanced Cancer

NCT01394016 | Completed Phase 1 Results

• 2 other identifiers: 13199I3Y-MC-JPBA
• Study Type: interventional
• Target: 225
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to determine a safe dose of Abemaciclib to be given to participants with advanced cancer and to determine any side effects that may be associated with Abemaciclib in this population. Efficacy measures will be used to assess the activity of Abemaciclib in this population.

Conditions

Advanced Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Clinically Significant Effects

  The number of participants with clinically significant findings in the study were reported in this outcome measure.

  Baseline up to 233 weeks

Secondary Outcomes (4)

• Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR)

  Baseline through Study Completion (Up to 285 weeks)

• Pharmacokinetics (PK): Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib

  Day 28 (0, 1, 2, 4, 6, 8, 10, 24 hours post-dose) of Cycle 1

• PK: Area Under the Steady State Plasma Concentration-time Curve Over 24 Hours (AUC 0-24hr,ss) of Abemaciclib

  Day 28 (0, 1, 2, 4, 6, 8, 10, 24 hours post-dose) of Cycle 1

• Part A: Recommended Dose for Phase 2 Studies

  Baseline through Study Completion (Up to 285 weeks)

Study Arms (1)

Abemaciclib

EXPERIMENTAL

Participants received oral Abemaciclib administered on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as appropriate on Day -3 and then on Days 1 to 27. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. Participants belonging to different Parts received the study drug as specified below: Part A: 50 mg/100 mg/150 mg/225 mg every 24 hours (Q24H) or 75mg/100 mg/150 mg/200 mg/275 mg every 12 hours (Q12H). Parts B, C, D, and E: 150 mg/200 mg Q12H. Part F: 150 mg Q12H. Part G: 200 mg Q12H along with 500 mg Fulvestrant administered intramuscularly.

Drug: Abemaciclib; Drug: Fulvestrant

Interventions

Abemaciclib DRUG

Administered orally.

Also known as: LY2835219

Abemaciclib

Fulvestrant DRUG

Fulvestrant is administered intramuscularly into the buttocks in Part G only.

Abemaciclib

Eligibility Criteria

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

You may qualify if:

• For all Parts (Dose escalation and expansion): The participant must be, in the judgment of the investigator, an appropriate candidate for experimental therapy either after available standard therapies have ceased to provide clinical benefit (Parts A, B, C, D, E and F) or in combination with fulvestrant (Part G only)
• For Dose Escalation (Part A): The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced and/or metastatic
• For Dose Expansion (Parts B, C, D, E, F and G): The participant must have histological or cytological evidence of one of the following cancers:
• Part B: Non-small cell lung cancer of any subtype that is advanced and/or metastatic
• Part C: Glioblastoma multiforme that has progressed or recurred after radiotherapy and/or chemotherapy
• Part D: Breast cancer that is advanced and/or metastatic
• Part E: Melanoma that is advanced and/or metastatic
• Part F: Colorectal Cancer
• Part G: Breast Cancer that is not only advanced and/or metastatic but also hormone receptor positive
• As defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma
• For Parts A and G: Have measurable or nonmeasurable disease
• For Parts B, C, D, E and F: Have measurable disease
• Have given written informed consent prior to any study-specific procedures
• Have adequate hematologic, hepatic, and renal function
• Have a performance status less than or equal to 1 for Dose Escalation (Part A) and less than or equal to 2 for Dose Confirmation (Parts B, C, D, E, F and G) on the Eastern Cooperative Oncology Group (ECOG) scale

You may not qualify if:

• Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively
• Have a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), sudden cardiac death or sudden cardiac arrest
• 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)
• For Dose Escalation (Part A): Have central nervous system (CNS) malignancy or metastasis
• For Dose Confirmation (Parts B, D, E, F and G): Have CNS metastasis that is radiographically or clinically unstable less than 14 days prior to receiving study drug, regardless of whether they are receiving corticosteroids
• For Dose Confirmation (Part C): Have glioblastoma multiforme that is radiographically or clinically unstable less than 14 days prior to receiving study drug, regardless of whether they are receiving corticosteroids
• Have an acute leukemia
• Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug
• Females who are pregnant or lactating
• Have active bacterial, fungal, and/or known viral infection (for example, human immunodeficiency virus \[HIV\] antibodies, hepatitis B surface antigen \[HBSAg\], or hepatitis C antibodies) Screening is not required for enrollment

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (3)

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.

Santa Monica, California, 90404, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

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

San Antonio, Texas, 78229, United States

Location

Related Publications (2)

• Tate SC, Sykes AK, Kulanthaivel P, Chan EM, Turner PK, Cronier DM. A Population Pharmacokinetic and Pharmacodynamic Analysis of Abemaciclib in a Phase I Clinical Trial in Cancer Patients. Clin Pharmacokinet. 2018 Mar;57(3):335-344. doi: 10.1007/s40262-017-0559-8.

  PMID: 28540640 DERIVED

• 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.

  PMID: 24919854 DERIVED

MeSH Terms

Interventions

abemaciclib; Fulvestrant

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

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

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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 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
• Expanded Access: Yes

Study Record Dates

• First Submitted: July 12, 2011
• First Posted: July 14, 2011
• Study Start: December 7, 2009
• Primary Completion: May 29, 2014
• Study Completion: April 12, 2022
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Locations

US (3)