Clinical Trials /

A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-small Cell Lung Cancer, or Melanoma That Has Spread to the Brain

NCT02308020

Description:

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as abemaciclib in participants with hormone receptor positive breast cancer, non-small cell lung cancer (NSCLC), or melanoma that has spread to the brain.

Related Conditions:
  • Breast Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-small Cell Lung Cancer, or Melanoma That Has Spread to the Brain
  • Official Title: A Phase 2 Study of Abemaciclib in Patients With Brain Metastases Secondary to Hormone Receptor Positive Breast Cancer, Non-small Cell Lung Cancer, or Melanoma

Clinical Trial IDs

  • ORG STUDY ID: 15450
  • SECONDARY ID: I3Y-MC-JPBO
  • SECONDARY ID: 2014-004010-28
  • NCT ID: NCT02308020

Conditions

  • Breast Cancer
  • Non-small Cell Lung Cancer
  • Melanoma
  • Brain Metastases

Interventions

DrugSynonymsArms
AbemaciclibLY2835219Part A: HER2+ Breast Cancer

Purpose

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as abemaciclib in participants with hormone receptor positive breast cancer, non-small cell lung cancer (NSCLC), or melanoma that has spread to the brain.

Trial Arms

NameTypeDescriptionInterventions
Part A: HER2+ Breast CancerExperimentalParticipants with HR+, HER2+ breast cancer. 200 milligrams (mg) abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
  • Abemaciclib
Part B: HER2- Breast CancerExperimentalParticipants with HR+, HER2- breast cancer. 200 mg abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
  • Abemaciclib
Part C: Surgical ResectionExperimentalParticipants with HR+ breast cancer, NSCLC, or melanoma with intracranial lesions for which surgical resection is clinically indicated. 200 mg abemaciclib given orally once every 12 hours for 5-14 days prior to surgical resection. Dosing may resume following wound healing on a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
  • Abemaciclib
Part D: NSCLCExperimentalParticipants with NSCLC. 200 milligrams mg (150 mg for participants receiving concurrent gemcitabine or pemetrexed) abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
  • Abemaciclib
Part E: MelanomaExperimentalParticipants with melanoma. 200 milligrams mg abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
  • Abemaciclib
Part F: HR+ Breast Cancer, NSCLC, or MelanomaExperimentalParticipants with HR+ breast cancer, NSCLC, or melanoma and leptomeningeal metastases. 200 milligrams mg abemaciclib given orally once every 12 hours on days 1-21 of a 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
  • Abemaciclib

Eligibility Criteria

        Inclusion Criteria:

          -  Have brain metastases secondary to hormone receptor positive breast cancer, NSCLC, or
             melanoma.

          -  Have either human epidermal growth factor receptor 2 positive (HER2+) (Study Part A)
             or HER2- (Study Part B) breast cancer.

          -  Participants in Study Part C must have HR+ breast cancer, NSCLC, or melanoma with
             brain lesions clinically indicated for surgical resection as well as consent to
             provide tissue for drug concentration determination after 5 to 14 days of study drug
             dosing.

          -  Participants in Part D must have NSCLC of any subtype.

          -  Participants in Part E must have melanoma of any subtype.

          -  Participants in Part F must have HR+ breast cancer, NSCLC, or melanoma with
             leptomeningeal metastases.

          -  For Parts A, B, D, and E: Must have at least 1 measurable brain lesion ≥10 millimeters
             (mm) in the longest diameter (LD).

          -  For Part C (surgical): Have metastatic brain lesion(s) for which surgical resection is
             clinically indicated.

          -  Have completed local therapy (surgical resection, WBRT, or SRS) ≥14 days prior to
             initiating abemaciclib and recovered from all acute effects.

          -  If receiving concomitant corticosteroids, must be on a stable or decreasing dose for
             at least 7 days prior to the baseline Gd-MRI.

          -  Have a Karnofsky performance status of ≥70.

          -  Have a life expectancy ≥12 weeks.

          -  For HR+ breast cancer participants in part A, B, C, and F: If currently receiving
             endocrine therapy, a participant may continue to receive the same endocrine therapy
             provided that extracranial disease is stable for at least 3 months and central nervous
             system (CNS) disease progression has occurred while on this endocrine therapy. If
             these conditions are not met, participants must discontinue endocrine therapy prior to
             initiation of abemaciclib.

          -  For HER2+ breast cancer participants in parts A, C, and F: participants may receive
             concurrent treatment (ongoing or initiated simultaneously with abemaciclib) with IV
             trastuzumab.

          -  For NSCLC participants in parts C, D, and F: if currently receiving gemcitabine or
             pemetrexed (single-agent or in combination with another therapy), a participant may
             continue to receive 1 of these 2 therapies provided that extracranial disease is
             stable for at least 6 weeks and CNS disease progression has occurred while on this
             therapy.

          -  Have adequate organ function.

        Exclusion Criteria:

          -  Require immediate local therapy, including but not limited to WBRT, SRS, or surgical
             resection, for treatment of brain metastases.

          -  Are taking concurrent enzyme-inducing antiepileptic drugs (EIAED).

          -  Have evidence of significant (ie, symptomatic) intracranial hemorrhage.

          -  For Parts A, B, C, D, E: Have evidence of leptomeningeal metastases. Note: discrete
             dural metastases are permitted.

          -  Have experienced >2 seizures within 4 weeks prior to study entry.

          -  For Parts A, B, D, E, and F: Have previously received treatment with any cyclin
             dependent kinase 6 (CDK6) inhibitor. For Part C participants may have received prior
             palbociclib or ribociclib, but not abemaciclib treatment.

          -  Have known contraindication to Gd-MRI.

          -  Have a preexisting chronic condition resulting in persistent diarrhea.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR)
Time Frame:Baseline to Objective Disease Progression (Approximately 6 Months)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants with CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR)
Time Frame:Baseline to Earliest Objective Progression or Start of New Anticancer Therapy (Approximately 6 Months)
Safety Issue:
Description:
Measure:Duration of CR and PR: Duration of Intracranial Response (DOIR)
Time Frame:Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death from Any Cause (Approximately 6 Months)
Safety Issue:
Description:
Measure:Proportion of Participants with BOIR of CR, PR, or SD: Intracranial Disease Control Rate (IDCR)
Time Frame:Baseline to Disease Progression or Start of New Anticancer Therapy (Approximately 6 Months)
Safety Issue:
Description:
Measure:Proportion of Participants with BOIR of CR, PR, or SD with Duration of SD for at Least 6 Months: Intracranial Clinical Benefit Rate (ICBR)
Time Frame:Baseline to Disease Progression or Start of New Anticancer Therapy (Approximately 6 Months)
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:Baseline to Death from Any Cause (Approximately 18 Months)
Safety Issue:
Description:
Measure:Percentage of Participants with a Best Response of CR or PR: Objective Response Rate (ORR)
Time Frame:Baseline to Disease Progression (Approximately 6 Months)
Safety Issue:
Description:
Measure:Proportion of Participants with a Best Overall Response of CR, PR, or SD: Disease Control Rate (DCR)
Time Frame:Baseline to Disease Progression or Start of New Anticancer Therapy (Approximately 6 Months)
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:Baseline to Objective Disease Progression or Death from Any Cause (Approximately 6 Months)
Safety Issue:
Description:
Measure:Change from Baseline to End of Study in Neurologic Symptoms on the MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) Scale
Time Frame:Baseline, End of Study (Approximately 6 Months)
Safety Issue:
Description:
Measure:Pharmacokinetics (PK): Minimum Concentration (Cmin) of Abemaciclib and its Metabolites
Time Frame:Cycle 1 through Cycle 4 (Approximately 3 Months)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eli Lilly and Company

Last Updated

July 28, 2017