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

Study Overview
=================
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.

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

Conditions
-----------------
Non-Small Cell Lung Cancer Stage IV

Intervention / Treatment
-----------------
* Drug: Abemaciclib
* Drug: Docetaxel


Participation Criteria
=================
Eligibility 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 measurable 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abemaciclib<br>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<br>* Administered orally<br>* Other names: LY2835219;|
| Active Comparator: Docetaxel<br>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<br>* Administered IV<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | 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. | Baseline to Objective Progression or Death from Any Cause ( Up To 6 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Clearance of Abemaciclib | Pharmacokinetics (PK): Clearance of Abemaciclib | 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 | PK: Volume of Distribution of Abemaciclib | 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 | 
| Overall Survival (OS) | 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. | Baseline to Date of Death from Any Cause (Up To 28 Months) | 
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) | 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. | Baseline to Objective Progression (Up To 6 Months) | 
| Percentage of Participants Who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR): Disease Control Rate (DCR) | 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. | Baseline through Measured Progressive Disease or Death Due to Any Cause (Up To 6 Months) | 
| Time to Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status of >/=2 | 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 | Randomization to ECOG PFS of >/=2 (Up To 11.5 Months) | 
| Change From Baseline in MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) Scores | 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. | Baseline through End of Study (Up To 6 Months) | 
| Change From Baseline in EuroQol 5-Dimensional 5-Level (EQ-5D-5L) Questionnaire EQ VAS Overall Self-rated Health Score | 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. | Baseline to Measured Progressive Disease (Up To 6 Months) | 
| Change From Baseline in EuroQol 5-Dimensional 5-Level (EQ-5D-5L) Questionnaire Index Value | 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. | Baseline to Measured Progressive Disease (Up To 6 Months) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
patient reported outcomes (PRO), patient focused outcomes (PFO), biomarkers, CDK 4 and 6