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

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.

Brief Title

Categories

Lung & Chest Cancers

Cancer

Lung

COVID-19

Asthma and Other Respiratory Diseases

Completion Date

2020-07-29

Completion Date Type

Actual

Conditions

Non-Small Cell Lung Cancer Stage IV

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.

Inclusion 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.

Gender

All

Gender Based

false

Keywords

patient reported outcomes (PRO)

patient focused outcomes (PFO)

biomarkers

CDK 4 and 6

Healthy Volunteers

No

Last Update Post Date

Fri, 08/13/2021 - 12:00

Last Update Post Date Type

Actual

Last Update Submit Date

Mon, 07/26/2021 - 12:00

Minimum Age

18 Years

NCT Id

NCT02450539

Org Class

Industry

Org Full Name

Eli Lilly and Company

Org Study Id

15806

Overall Status

Completed

Phases

Phase 2

Primary Completion Date

Fri, 03/31/2017 - 12:00

Primary Completion Date Type

Actual

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

Primary Outcomes

Outcome Description

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.

Outcome Measure

Progression Free Survival (PFS)

Outcome Time Frame

Baseline to Objective Progression or Death from Any Cause ( Up To 6 Months)

Secondary Ids

Secondary Id

I3Y-MC-JPBX

Secondary Id

2014-004832-20

Secondary Outcomes

Outcome Description

Pharmacokinetics (PK): Clearance of Abemaciclib

Outcome 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

Outcome Measure

Pharmacokinetics (PK): Clearance of Abemaciclib

Outcome Description

PK: Volume of Distribution of Abemaciclib

Outcome 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

Outcome Measure

PK: Volume of Distribution of Abemaciclib

Outcome Description

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.

Outcome Time Frame

Baseline to Date of Death from Any Cause (Up To 28 Months)

Outcome Measure

Overall Survival (OS)

Outcome Description

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.

Outcome Time Frame

Baseline to Objective Progression (Up To 6 Months)

Outcome Measure

Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])

Outcome Description

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.

Outcome Time Frame

Baseline through Measured Progressive Disease or Death Due to Any Cause (Up To 6 Months)

Outcome Measure

Percentage of Participants Who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR): Disease Control Rate (DCR)

Outcome Description

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

Outcome Time Frame

Randomization to ECOG PFS of >/=2 (Up To 11.5 Months)

Outcome Measure

Time to Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status of >/=2

Outcome Description

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.

Outcome Time Frame

Baseline through End of Study (Up To 6 Months)

Outcome Measure

Change From Baseline in MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) Scores

Outcome Description

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.

Outcome Time Frame

Baseline to Measured Progressive Disease (Up To 6 Months)

Outcome Measure

Change From Baseline in EuroQol 5-Dimensional 5-Level (EQ-5D-5L) Questionnaire EQ VAS Overall Self-rated Health Score

Outcome Description

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.

Outcome Time Frame

Baseline to Measured Progressive Disease (Up To 6 Months)

Outcome Measure

Change From Baseline in EuroQol 5-Dimensional 5-Level (EQ-5D-5L) Questionnaire Index Value