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A Study of Abemaciclib (LY2835219) in Participants With Previously Treated KRAS Mutated Lung Cancer (JUNIPER)

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ClinicalTrials.gov Identifier: NCT02152631
Recruitment Status : Active, not recruiting
First Posted : June 2, 2014
Results First Posted : December 12, 2018
Last Update Posted : October 29, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE May 23, 2014
First Posted Date  ICMJE June 2, 2014
Results First Submitted Date  ICMJE August 23, 2018
Results First Posted Date  ICMJE December 12, 2018
Last Update Posted Date October 29, 2019
Actual Study Start Date  ICMJE October 3, 2014
Actual Primary Completion Date September 15, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 16, 2018)
Overall Survival (OS) [ Time Frame: From Randomization Date to Date of Death from Any Cause (Up to 32 Months) ]
OS defined as from randomization date to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.
Original Primary Outcome Measures  ICMJE
 (submitted: May 29, 2014)
  • Progression Free Survival (PFS) [ Time Frame: Baseline to Objective Progression or Death from Any Cause (Estimated Up to 34 Months) ]
  • Overall Survival (OS) [ Time Frame: Baseline to Date of Death from Any Cause (Estimated Up to 34 Months) ]
Change History Complete list of historical versions of study NCT02152631 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 16, 2018)
  • Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) [ Time Frame: From Randomization Date to Objective Progression (Up to 32 Months) ]
    ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR 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.
  • Progression Free Survival (PFS) [ Time Frame: From Randomization Date until Disease Progression or Death from Any Cause (Up to 32 Months) ]
    PFS defined as the from randomization date to the first evidence of disease progression as defined by RECIST v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
  • Change From Baseline in MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) Score [ Time Frame: From Randomization Date through End of Study (Up to 32 Months) ]
    The MDASI-LC included 22 items + 3 additional trial-specific items, resulting in 6 collected and reported single-construct scores including core symptoms (13-item), interference (6-item), lung cancer (3-item), and trial-specific single outcomes for headache, diarrhea, and rash. A 2-construct composite core + lung cancer symptom (16-item) score was calculated. Data for all 7 scores 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). Mixed Model Repeated Measure (MMRM) regression with covariates for treatment, visit, treatment*visit, and baseline score predicted between-group Least Squares (LS) mean differences from baseline. Group-level negative change from baseline indicated group improvement.
  • Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve During 1 Dosing Interval at Steady State [ Time Frame: Day 1 of Cycle 1 through Cycle 3 (28 Day Cycles) ]
    PK is determined by the area under the plasma concentration versus time curve during 1 dosing interval at steady state
  • Change From Baseline in European Quality of Life - 5 Dimensions - 5 Level (EQ-5D-5L) Score [ Time Frame: From Randomization Date through End of Study (Up to 32 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 United Kingdom (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. LS Mean value was controlled for Treatment, visit, Treatment*Visit and baseline.
  • Resource Utilization: Percentage of Participants Who Are Hospitalized [ Time Frame: From Randomization Date through End of Study (Up to 32 Months) ]
    Resource utilization is the percentage of participants who was hospitalized.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2014)
  • Proportion of Participants Achieving Either Complete or Partial Response (Overall Response Rate) [ Time Frame: Baseline to Objective Progression or Death from Any Cause (Estimated Up to 34 Months) ]
  • Change From Baseline in MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) Score [ Time Frame: Baseline through End of Study (Estimated Up to 34 Months) ]
  • Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2835219 [ Time Frame: Cycle 1 through Cycle 3 (28 Day Cycles) ]
  • Change From Baseline in European Quality of Life - 5 Dimensions - 5 Level (EQ-5D-5L) Score [ Time Frame: Baseline through End of Study (Estimated Up to 34 Months) ]
  • Resource Utilization: Percentage of Participants Who Are Hospitalized [ Time Frame: Baseline through End of Study (Estimated Up to 34 Months) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Abemaciclib (LY2835219) in Participants With Previously Treated KRAS Mutated Lung Cancer
Official Title  ICMJE JUNIPER: A Randomized Phase 3 Study of Abemaciclib Plus Best Supportive Care Versus Erlotinib Plus Best Supportive Care in Patients With Stage IV NSCLC With a Detectable KRAS Mutation Who Have Progressed After Platinum-Based Chemotherapy
Brief Summary The main purpose of this study is to evaluate how safe and effective the study drug known as abemaciclib is in participants with lung cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Abemaciclib
    Administered orally
    Other Name: LY2835219
  • Drug: Erlotinib
    Administered orally
Study Arms  ICMJE
  • Experimental: Abemaciclib
    200 milligrams (mg) abemaciclib administered, orally, every 12 hours plus best supportive care (BSC) on Days 1 to 28 (28 day cycles).
    Intervention: Drug: Abemaciclib
  • Active Comparator: Erlotinib
    150 mg erlotinib administered, orally, every 24 hours plus BSC on Days 1 to 28 (28 day cycles).
    Intervention: Drug: Erlotinib
Publications * Goldman JW, Shi P, Reck M, Paz-Ares L, Koustenis A, Hurt KC. Treatment Rationale and Study Design for the JUNIPER Study: A Randomized Phase III Study of Abemaciclib With Best Supportive Care Versus Erlotinib With Best Supportive Care in Patients With Stage IV Non-Small-Cell Lung Cancer With a Detectable KRAS Mutation Whose Disease Has Progressed After Platinum-Based Chemotherapy. Clin Lung Cancer. 2016 Jan;17(1):80-4. doi: 10.1016/j.cllc.2015.08.003. Epub 2015 Aug 18.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 16, 2018)
453
Original Estimated Enrollment  ICMJE
 (submitted: May 29, 2014)
550
Estimated Study Completion Date  ICMJE September 20, 2020
Actual Primary Completion Date September 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have confirmed diagnosis of stage IV non-small cell lung cancer (NSCLC) according to the American Joint Committee on Cancer Staging Handbook.
  • Determined to have detectable mutations in codons 12 or 13 of the kirsten rat sarcoma (KRAS) oncogene by an investigational assay at the study central laboratory. A KRAS positive mutation result in codons 12 or 13 of the KRAS oncogene from tumor tissue per local laboratory will be permitted in no more than 10% of randomized participants.
  • Have progressed after platinum-based chemotherapy (with or without maintenance therapy) AND have received one additional therapy which may include an immune checkpoint inhibitor or other anti-cancer therapy for advanced and/or metastatic disease OR is judged by the physician as ineligible for further standard second-line chemotherapy. Participants who have progressed after platinum-based chemotherapy and an immune checkpoint inhibitor (immunotherapy) e.g. pembrolizumab or nivolumab alone or in combination with other agents are eligible.
  • Have measureable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  • Have a performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
  • Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug.

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), or sudden cardiac arrest.
  • Have the presence of unstable central nervous system (CNS) metastasis. History of CNS metastasis or stable CNS metastases is allowed (no longer requiring active therapy such as steroid medications). Participants with a history of CNS metastases must have a brain scan (for example, magnetic resonance imaging [MRI]) within 28 days of randomization to document stability, even if there have been no changes in symptoms.
  • Have previously completed or withdrawn from this study or any other study investigating a cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) inhibitors, or have received treatment with a prior CDK4 and CDK6 inhibitors.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Austria,   Brazil,   Canada,   China,   France,   Germany,   Greece,   Israel,   Italy,   Japan,   Korea, Republic of,   Poland,   Puerto Rico,   Romania,   Russian Federation,   Spain,   Taiwan,   Turkey,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02152631
Other Study ID Numbers  ICMJE 15296
I3Y-MC-JPBK ( Other Identifier: Eli Lilly and Company )
2013-004662-33 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Eli Lilly and Company
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP