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A Study of Abemaciclib (LY2835219) in Participants With Stage IV Squamous Non-small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT02450539
Recruitment Status : Active, not recruiting
First Posted : May 21, 2015
Results First Posted : June 25, 2018
Last Update Posted : June 25, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The main purpose of this study is to evaluate the effectiveness of the study drug known as abemaciclib versus docetaxel in participants with stage IV squamous non-small cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Stage IV Drug: Abemaciclib Drug: Docetaxel Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 159 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase 2 Study of Abemaciclib (LY2835219) Versus Docetaxel in Patients With Stage IV Squamous Non-Small Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy
Study Start Date : August 2015
Actual Primary Completion Date : March 2017
Estimated Study Completion Date : July 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Abemaciclib
200 milligram (mg) abemaciclib given orally every 12 hours (Q12H) on days 1 to 21 of each 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Active Comparator: Docetaxel
75 milligram per meter squared (mg/m²) docetaxel given intravenously (IV) on day 1 of each 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.
Drug: Docetaxel
Administered IV




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Baseline to Objective Progression or Death from Any Cause ( Up To 6 Months) ]
    PFS was defined as time from the date of randomization to the date of investigator-determined disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause. Progressive disease (PD) was defined as at least a 20% increase in the sum of the longest diameters (LD) of target lesions, with reference the smallest sum on study and an absolute increase of at least 5mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant was not known to have died or have objective progression, PFS time will be censored at the day of their last radiographic tumor assessment (if available) or date of randomization if no post baseline radiographic assessment is available.


Secondary Outcome Measures :
  1. Pharmacokinetics (PK): Clearance of Abemaciclib [ Time Frame: Cycle (C) 1 Day (D) 1: Pre-dose; C1D8: 4 and 7 hr Post-dose; C2D1: Pre-dose and 3 hr Post-dose; C3 and C4 D1:Pre-dose ]
    Pharmacokinetics (PK): Clearance of Abemaciclib

  2. PK: Volume of Distribution of Abemaciclib [ Time Frame: Cycle (C) 1 Day (D) 1: Pre-dose; C1D8: 4 and 7 hr Post-dose; C2D1: Pre-dose and 3 hr Post-dose; C3 and C4 D1:Pre-dose ]
    PK: Volume of Distribution of Abemaciclib

  3. Overall Survival (OS) [ Time Frame: Baseline to Date of Death from Any Cause (Approximately 11 Months) ]
    OS was defined as the time from randomization to the date of death due to any cause. For each participant who is not known to have died as the data inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.

  4. Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) [ Time Frame: Baseline to Objective Progression (Up To 6 Months) ]
    Overall response was defined as the percentage of randomized participants achieving a best overall response (BoR) 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.

  5. Percentage of Participants Who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR): Disease Control Rate (DCR) [ Time Frame: Baseline through Measured Progressive Disease or Death Due to Any Cause (Up To 6 Months) ]
    DCR is the percentage of randomized participants who achieved a complete response, partial response or stable disease using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. 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 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. Stable disease was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions.

  6. Time to Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status of >/=2 [ Time Frame: Randomization to ECOG PFS of >/=2 (Up To 11.5 Months) ]

    Worsening of ECOG performance status is the duration from randomization to ECOG PFS of >/=2. Participants without an ECOG PFS >/=2 are censored at last adequate post baseline ECOG Performance Status or randomization date (whichever is last).

    The ECOG Performance Status:0 - Fully active, able to carry on all pre-disease performance without restriction,1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, 2 - Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours,3 - Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours, 4 - Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair, 5 - Dead


  7. Change From Baseline in MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) Scores [ Time Frame: Baseline through End of Study (Up To 6 Months) ]
    MDASI-LC included 33 items:6 interference and 27 symptom(3 lung-cancer (LC),8 brain tumor (BT),and 3 study-specific(headache,diarrhea, and rash).Analyzed endpoints were 9 constructs:3 single-items (headache,diarrhea,and rash) and 6 composites(interference+core,LC,core+LC,BT, and core+LC worst 5 baseline).Data for all 9 constructs were collected by an 11-point numeric rating scale anchored at 0(not present or does not interfere) and 10(as bad as you can imagine or interfered completely).The measurement range was 10 (maximum score-minimum score). Between-group difference in regression-predicted change from baseline were estimated for each specified construct. MMRM models included independent variables treatment,visit, treatment*visit,and baseline score. Group-level negative change from baseline indicated group improvement.

  8. Change From Baseline in EuroQol 5-Dimensional 5-Level (EQ-5D-5L) Questionnaire EQ VAS Overall Self-rated Health Score [ Time Frame: Baseline to Measured Progressive Disease (Up To 6 Months) ]
    The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Overall self-rated health was measured with a vertical 20 cm visual analog scale (VAS) anchored at 0 (worst health) and ranged through 100 (best health). Between-group differences in regression-predicted change from baseline score were estimated for VAS scores. MMRM models included independent variables treatment, visit, treatment*visit, and baseline score. Group-level negative change from baseline indicated group improvement.

  9. Change From Baseline in EuroQol 5-Dimensional 5-Level (EQ-5D-5L) Questionnaire Index Value [ Time Frame: Baseline to Measured Progressive Disease (Up To 6 Months) ]
    There are 5 response levels on a good-to-bad continuum of 1-5 corresponding to none, slight, moderate, severe, and extreme/unable to.The EuroQol-developed crosswalk method was used to convert the EQ-5D-5L,using UK weights,health dimensions(mobility,self-care,usual activities,pain/discomfort, and anxiety/depression) into a single index value;the dimensions are not separately scored.The index is marked missing when ≥1 dimensions are missing.The index scores for the response patterns were anchored on full health to dead with negative values assigned to response patterns/health states considered worse than death.The best pattern is assigned the index value of 1.0; the worst pattern is assigned an index value of -0.594. Between-group differences in regression-predicted change from baseline score were estimated for the index .MMRM models included independent variables treatment, visit, treatment*visit, and baseline score.Group-level negative change from baseline indicated group improvement.



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

Inclusion Criteria:

  • Confirmed diagnosis of stage IV NSCLC.
  • Have progressed during or after platinum-based chemotherapy for advanced disease.
  • Have not received prior treatment with docetaxel.
  • Have availability of adequate formalin-fixed paraffin-embedded (FFPE) tumor derived material.
  • Have adequate organ function including hematology, renal, and liver.
  • Have good performance score (0-1).
  • Have measureable disease per RECIST 1.1.
  • Agree to use a reliable medically approved method of birth control.

Exclusion Criteria:

  • Have received prior treatment with any cyclin dependent kinase (CDK) 4 and 6 inhibitor or participated in a clinical trial with a CDK 4 and 6 inhibitor and the treatment administered is not known.
  • Are currently receiving treatment in a clinical trial involving an investigational product or non-approved use of a drug or device.
  • Have the presence of unstable central nervous system (CNS) metastasis.
  • Have had major surgery (excluding biopsy) < 28 days of the initial dose of study drug.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02450539


  Show 51 Study Locations
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:
Study Protocol  [PDF] March 27, 2015
Statistical Analysis Plan  [PDF] June 9, 2015


Additional Information:
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02450539     History of Changes
Other Study ID Numbers: 15806
I3Y-MC-JPBX ( Other Identifier: Eli Lilly and Company )
2014-004832-20 ( EudraCT Number )
First Posted: May 21, 2015    Key Record Dates
Results First Posted: June 25, 2018
Last Update Posted: June 25, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com.

This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.


Keywords provided by Eli Lilly and Company:
patient reported outcomes (PRO)
patient focused outcomes (PFO)
biomarkers
CDK 4 and 6

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action