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Completed

NCT Number: NCT02187783

LEE011 for Patients With CDK4/6 Pathway Activated Tumors (SIGNATURE)

The purpose of this signal seeking study was to determine whether treatment with LEE011 demonstrates sufficient efficacy in CDK4/6 pathway activated solid tumors and/or hematologic malignancies to warrant further study.

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Key information

Conditions

Tumors With CDK4/6 Pathway Activation Adenoma Adnexal Diseases Breast Diseases Breast Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Hematologic Diseases Hematologic Neoplasms Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Lymphatic Diseases Lymphoma Lymphoproliferative Disorders Mesothelioma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Neoplasms, Mesothelial Ovarian Diseases Ovarian Neoplasms Skin Diseases Skin and Connective Tissue Diseases Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Alabama at Birmingham, Birmingham, Alabama, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patient had a confirmed diagnosis of a select solid tumor (except breast cancer (however, triple negative was included), liposarcoma, CRPC, melanoma and teratoma) or hematological malignancy (except mantle cell lymphoma).
  • Patient must have been pre-identified as having a tumor with CDK4 amplification or mutation, CDK6 amplification or mutation, Cyclin D1 (CCND1) amplification, Cyclin D3 (CCND3) amplification, or p16 (CDKN2A) mutation
  • Patient had received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission.
  • Patient had progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines.
  • Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

Exclusion criteria

  • Patients had received prior treatment with LEE011.
  • Patient had clinically significant resting bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval > 109 msec, or QTcF > 450 msec.
  • Patients had primary CNS tumor or CNS tumor involvement
  • Patient had received chemotherapy or anticancer therapy ≤ 4 weeks prior to starting study drug

Treatment and study plan

LEE011

Drug

Study drug was provided in 200 mg and 50 mg hard gelatin capsules to be taken orally

Primary outcomes

  1. Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments

    Time frame: Baseline up ≥16 weeks up to approximately 36 months

    Clinical benefit (CB) for patients with solid tumors were assessed using RECIST 1.1 and included responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) for ≥ 16 weeks. CR and PR (for solid tumors) required a confirmation at least 4 weeks after the initial response observation. For hematologic tumors other appropriate hematological response criteria was applied. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 mm, PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD=At least a 20% increase in the sum of diameter of all measured target lesions and also demonstrate an absolute increase of at least 5 mm. FAS

  2. Clinical Benefit Rate (CBR) of ≥ 16 Weeks FAS

    Time frame: Baseline and ≥ 16 weeks up to approximately 36 months

    CBR was determined by local, Investigator assessment for each tumor assessment and defined as responses of CR + PR + SD for ≥ 16 weeks. CR and PR (for solid tumors) required a confirmation at least 4 weeks after the initial response observation. For hematologic tumors other appropriate hematological response criteria was applied. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 mm, PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD=At least a 20% increase in the sum of diameter of all measured target lesions and also demonstrate an absolute increase of at least 5 mm FAS

  3. Overall Response Rate (ORR) ≥ 16 Weeks. FAS

    Time frame: Baseline and ≥ 16 weeks up to approximately 36 months

    ORR was determined by local, Investigator assessment for each tumor assessment and defined as responses of CR+PR ≥ 16 weeks. FAS

Secondary outcomes

  1. Progression Free Survival (PFS)

    Time frame: Every 8 weeks until death, assessed up to 24 months

    Progression-free survival (PFS) is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause within 30 days of the last dose. If a subject has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Progressive disease is defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (Note: the appearance of one or more new lesions is also considered progression)

  2. Overall Survival (OS)

    Time frame: Baseline up to approximately 36 months

    Number of participants Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause.

  3. Number of Days for Duration of Response for Responders

    Time frame: Baseline up to approximately 36 months

    Duration of response (DOR) is defined as time from the first documented response to the date first documented disease progression or relapse or death due to any cause. For patients with solid tumors the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 8 - LEE011 for Patients With CDK4/6 Pathway Activated Tumors

Acronym: SIGNATURE

Important dates

Study start
2014
Primary completion
2018
Study completion
2018
First posted
Jul 11, 2014
Registry last updated
Jul 18, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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