A Phase Ib/II Study of LEE011 in Combination With MEK162 in Patients With NRAS Mutant Melanoma
NCT ID: NCT01781572
Last Updated: 2020-12-07
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1/PHASE2
102 participants
INTERVENTIONAL
2013-06-30
2018-02-20
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Phase Ib
The phase Ib is the dose escalation part where successive cohorts of 3-6 newly enrolled patients receiving various dose pairs considering the recommendation from an adaptive BLRM incorporating the EWOC principle until MTD(s)/RP2D is defined. If multiple alternate dosing schedules are explored in parallel, the allocation of patients will proceed in an alternating fashion. Approximately 40 patients are expected to be treated during the phase Ib part of the study.
Dosing Schedule 1: MEK162 administered orally twice daily on a continuous dosing schedule. LEE011 administered orally once daily for 21 days followed by a 1 week break (28-day cycle).
Dosing Schedule 2: MEK162 administered orally twice daily and LEE011 administered orally once daily for 3 weeks followed by a 1 week break (28-day cycle).
Dosing Schedule 3: MEK162 administered orally twice daily and LEE011 administered once daily for 2 weeks followed by a 1 week break (21-day cycle).
LEE011
LEE011 will be administered orally once daily
MEK162
MEK162 will be administered orally twice daily
Phase II
The Phase II part will begin once the MTD(s)/RP2D have been determined in the Phase Ib in order to assess antitumor activity of the LEE011and MEK162 combination. Patients enrolled in the Phase II part of the study are required to have measurable disease. Approximately 40 patients will be treated in this part.
Phase II part will begin at the RP2D on the chosen schedule in order to assess antitumor activity of the LEE011 and MEK162 combination.
LEE011
LEE011 will be administered orally once daily
MEK162
MEK162 will be administered orally twice daily
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
LEE011
LEE011 will be administered orally once daily
MEK162
MEK162 will be administered orally twice daily
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Patients enrolled into phase Ib may be enrolled with evaluable disease only. Patients enrolled into the phase II expansion must have at least one measurable lesion as defined by RECIST 1.1 criteria for solid tumors.
* Patients must have adequate organ function, as defined by the following parameter
1. Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L.
2. Hemoglobin (Hgb) ≥ 9 g/dL.
3. Platelets ≥ 75 x 109/L without transfusions within 21 days before 1st treatment.
4. PT/INR and aPTT ≤ 1.5 ULN.
5. Serum creatinine ≤1.5 ULN.
6. Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN).
7. AST and ALT ≤ 3 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT ≤ 5 x ULN.
Exclusion Criteria
* Uncontrolled arterial hypertension despite medical treatment
* Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
1. Left ventricular ejection fraction (LVEF) \< 50% as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO).
2. Congenital long QT syndrome or family history of unexpected sudden cardiac death.
3. QTcF corrected with Frederica's or Bazett's formula QTcB \>450 ms for males and \>470 ms for females on screening ECG.
4. Angina pectoris ≤ 3 months prior to starting study drug
5. Acute myocardial infarction ≤ 3 months prior to starting study drug
6. Clinically significant resting bradycardia
7. History or presence of ventricular tachyarrhythmia
8. Unstable atrial fibrillation (ventricular response \>100 bpm)
9. Complete left bundle branch block
10. Right bundle branch block and left anterior hemi block (bifascicular block)
11. Obligate use of a cardiac pacemaker or implantable cardioverter defibrillator
12. Any other clinically significant heart disease
* Patients who are currently receiving treatment with agents that are known to cause QTc prolongation in humans.
* Patients who have neuromuscular disorders that are associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) or elevated baseline CK levels (≥ Grade 2)
* Patients who are currently receiving treatment with agents that are metabolized predominantly through CYP3A4 and that have a narrow therapeutic window.
* Patients with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (i.e. uncontrolled diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection).
* History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Pfizer
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Pfizer CT.gov Call Center
Role: STUDY_DIRECTOR
Pfizer
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of California, Dept of Oncology
San Francisco, California, United States
California Pacific Medical Center Onc Dept
San Francisco, California, United States
Karmanos Cancer Institute Dept of Oncology
Detroit, Michigan, United States
Memorial Sloan Kettering Cancer Center Dept Oncology
New York, New York, United States
Columbia University Medical Center- New York Presbyterian Onc Dept.
New York, New York, United States
Vanderbilt University Medical Center SC - Dept of Oncology .
Nashville, Tennessee, United States
University of Texas/MD Anderson Cancer Center Dept of Onc.
Houston, Texas, United States
Pfizer Investigative Site 1003
North Sydney, New South Wales, Australia
Pfizer Investigative Site 1002
Westmead, New South Wales, Australia
Pfizer Investigator Site 1001
East Melbourne, Victoria, Australia
Pfizer Investigative Site 1050
Essen, , Germany
Pfizer Investigative Site 1053
Gera, , Germany
Pfizer Investigative Site 1052
Hanover, , Germany
Pfizer Investigative Site 1051
München, , Germany
Pfizer Investigative Site 1101
Napoli, , Italy
Pfizer Investigative Site 1151
Utrecht, The Netherlands, Netherlands
Pfizer Investigative Site 1150
Nijmegen, , Netherlands
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Schuler M, Zimmer L, Kim KB, Sosman JA, Ascierto PA, Postow MA, De Vos FYFL, van Herpen CML, Carlino MS, Johnson DB, Berking C, Reddy MB, Harney AS, Berlin JD, Amaria RN. Phase Ib/II Trial of Ribociclib in Combination with Binimetinib in Patients with NRAS-mutant Melanoma. Clin Cancer Res. 2022 Jul 15;28(14):3002-3010. doi: 10.1158/1078-0432.CCR-21-3872.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Statistical Analysis Plan
Document Type: Study Protocol
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
C4211005
Identifier Type: OTHER
Identifier Source: secondary_id
CMEK162X2114
Identifier Type: -
Identifier Source: org_study_id