Clinical trial NCT01394016: A Phase 1 Study of LY2835219 In Participants With Advanced Cancer
Official title: A Phase 1 Study of a CDK 4/6 Dual Inhibitor in Participants With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-07-14
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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
* Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy) with the exception of fulvestrant (for Part G only) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (treatment related toxicity resolved to baseline) except for residual alopecia
* Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
* Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug
* Females with child bearing potential must have a negative serum pregnancy test within 3 days of the first dose of study drug
* Have an estimated life expectancy of greater than or equal to 12 weeks
* Are able to swallow capsules

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Clinically Significant Effects
timeFrame: Baseline up to 233 weeks
Secondary outcomes:
measure: Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR)
timeFrame: Baseline through Study Completion (Up to 285 weeks)
measure: Pharmacokinetics (PK): Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib
timeFrame: Day 28 (0, 1, 2, 4, 6, 8, 10, 24 hours post-dose) of Cycle 1
measure: PK: Area Under the Steady State Plasma Concentration-time Curve Over 24 Hours (AUC 0-24hr,ss) of Abemaciclib
timeFrame: Day 28 (0, 1, 2, 4, 6, 8, 10, 24 hours post-dose) of Cycle 1
measure: Part A: Recommended Dose for Phase 2 Studies
timeFrame: Baseline through Study Completion (Up to 285 weeks)
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: 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.
state: California
city: Boston
country: United States
facility: 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
state: Massachusetts
city: San Antonio
country: United States
facility: 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
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.