Description:
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.
Title
- Brief Title: LEE011 for Patients With CDK4/6 Pathway Activated Tumors (SIGNATURE)
- Official 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
Clinical Trial IDs
- ORG STUDY ID:
CLEE011XUS03
- NCT ID:
NCT02187783
Conditions
- Tumors With CDK4/6 Pathway Activation
Interventions
| Drug | Synonyms | Arms |
|---|
| LEE011 | | LEE011 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| LEE011 | Experimental | LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days. | |
Eligibility Criteria
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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 |
Secondary Outcome Measures
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | Every 8 weeks until death, assessed up to 24 months |
| Safety Issue: | |
| Description: | 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) |
| Measure: | Overall Survival (OS) |
| Time Frame: | Baseline up to approximately 36 months |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Number of Days for Duration of Response for Responders |
| Time Frame: | Baseline up to approximately 36 months |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- Solid malignancy
- Hematologic malignancy
- Mutations
- Amplifications
- Signature
- CDK4
- CDK6
- CDK4/6
- Cyclin D1
- CCND,
- Cyclin D3
- p16 mutation
- CDKN2A
- LEE011
- Breast cancer
- Ovarian cancer
- Lymphoma
- Mesothelioma
- Pancreatic neuroendocrine
- Leukemia
- Tumor
Last Updated
July 18, 2019
