Locally Advanced or Metastatic NRAS Mutant MelanomaPhase 1/2NCT01781572
A Phase Ib/II Study of LEE011 in Combination With MEK162 in Patients With NRAS Mutant Melanoma
A Phase 1/2 study testing LEE011 and MEK162 in people with Locally Advanced or Metastatic NRAS Mutant Melanoma, run by Pfizer at 17 sites in 5 countries.
Trial summary
In the phase Ib, the primary purpose is to establish the maximum tolerated dose (MTD)(s)/recommended phase ll dose (RP2D) and schedule of LEE011 and MEK162 orally administered combination. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced or Metastatic NRAS Mutant Melanoma
- What is being tested?
- LEE011 and MEK162
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 17 sitesin 5 countries
- Study dates
- Jun 2013to 20 Feb 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
- 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
- Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L.
- Hemoglobin (Hgb) ≥ 9 g/dL.
- Platelets ≥ 75 x 109/L without transfusions within 21 days before 1st treatment.
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- PT/INR and aPTT ≤ 1.5 ULN.
- Serum creatinine ≤1.5 ULN.
- Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN).
- AST and ALT ≤ 3 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT ≤ 5 x ULN.
Who cannot join
- Presence of any brain metastases detected by MRI or CT with i.v. contrast of the brain at screening.
- Uncontrolled arterial hypertension despite medical treatment
- Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO).
- Congenital long QT syndrome or family history of unexpected sudden cardiac death.
- QTcF corrected with Frederica's or Bazett's formula QTcB >450 ms for males and >470 ms for females on screening ECG.
Show all 21Show fewer
- Angina pectoris ≤ 3 months prior to starting study drug
- Acute myocardial infarction ≤ 3 months prior to starting study drug
- Clinically significant resting bradycardia
- History or presence of ventricular tachyarrhythmia
- Unstable atrial fibrillation (ventricular response >100 bpm)
- Complete left bundle branch block
- Right bundle branch block and left anterior hemi block (bifascicular block)
- Obligate use of a cardiac pacemaker or implantable cardioverter defibrillator
- 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).
- Other protocol related inclusion/exclusion criteria may apply.
Trial locations and contacts
17 sites in 5 countries.
17 sites in 5 countries
United States7 sites
Karmanos Cancer Institute Dept of Oncology
Detroit, Michigan, 48201
University of Texas/MD Anderson Cancer Center Dept of Onc.
Houston, Texas, 77030-4009
Vanderbilt University Medical Center SC - Dept of Oncology .
Nashville, Tennessee, 37232
Memorial Sloan Kettering Cancer Center Dept Oncology
New York, New York, 10021
Columbia University Medical Center- New York Presbyterian Onc Dept.
New York, New York, 10032
University of California, Dept of Oncology
San Francisco, California, 94101
California Pacific Medical Center Onc Dept
San Francisco, California, 94120-7999
Germany4 sites
Pfizer Investigative Site 1050
Essen, 45147
Pfizer Investigative Site 1053
Gera, 07548
Pfizer Investigative Site 1052
Hanover, 30625
Pfizer Investigative Site 1051
München, 80336
Australia3 sites
Pfizer Investigator Site 1001
East Melbourne, Victoria
Pfizer Investigative Site 1003
North Sydney, New South Wales, 2060
Pfizer Investigative Site 1002
Westmead, New South Wales, 2145
Netherlands2 sites
Pfizer Investigative Site 1150
Nijmegen, 6525 GA
Pfizer Investigative Site 1151
Utrecht, The Netherlands, 3508 GA
About this study
Official title: A Phase Ib/II, Multicenter, Open Label, Study of LEE011 in Combination With MEK162 in Adult Patients With NRAS Mutant Melanoma
In the phase Ib, the primary purpose is to establish the maximum tolerated dose (MTD)(s)/recommended phase ll dose (RP2D) and schedule of LEE011 and MEK162 orally administered combination. Once the MTD(s)/RP2D have been determined for each tested schedule, additional patients will be enrolled in the phase II portion of the study at the RP2D on the chosen schedule in order to assess the anti-tumor activity of the combination in addition to continued evaluation of safety.
- Being tested
- LEE011, MEK162
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LEE011Drug
LEE011 will be administered orally once daily
MEK162Drug
MEK162 will be administered orally twice daily
| Study group | Role | What they receive |
|---|---|---|
| Phase Ib | Experimental | 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). Receives: Drug: LEE011; Drug: MEK162 |
| Phase II | Experimental | 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. Receives: Drug: LEE011; Drug: MEK162 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Dose Limiting Toxicities (Phase Ib)
To estimate the maximum tolerate doses (MTDs) and/or identify the RP2D and schedule of LEE011 and MEK162 combination. A dose-limiting toxicity (DLT) was defined as an AE or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first cycle of treatment with ribociclib and binimetinib.
Measured: first 28 days of treatment
Objective Response Rate (ORR) (Phase II)
ORR is the proportion of patients with best overall response of complete response (CR) or partial response (PR) by month 2 assessed according to RECIST 1.1 criteria. ORR is done to describe the anti-tumor activity of LEE011 and MEK162 combination. The primary analysis of the ORR was based on the Investigator's assessment of overall lesion responses per RECIST 1.1.
Measured: Approximately 12 months after the FPFV
Secondary outcomes (26)
Plasma Concentration-time Profile (AUCtau) of LEE011 (Phase Ib)
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Measured: Cycle 1 Day 1
Plasma Concentration-time Profile (AUCtau) of MEK162 (Phase Ib)
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Measured: Cycle 1 Day 1
Plasma Concentration-time Profile (AUCtau,ss) of LEE011 (Phase Ib)
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Measured: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (AUCtau,ss) of MEK162 (Phase Ib)
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Measured: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (Cmin,ss) of LEE011 (Phase Ib)
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Measured: For the 28-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 14
Plasma Concentration-time Profile (Cmin,ss) of MEK162 (Phase Ib)
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Measured: For the 28-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 14
Plasma Concentration-time Profile (Cmax) of LEE011 (Phase Ib)
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Measured: Cycle 1 Day 1
Plasma Concentration-time Profile (Cmax) of MEK162 (Phase Ib)
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Measured: Cycle 1 Day 1
Plasma Concentration-time Profile (Cmax,ss) of LEE011 (Phase Ib)
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Measured: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (Cmax,ss) of MEK162 (Phase Ib)
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Measured: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (Tmax) of LEE011 (Phase Ib)
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Measured: Cycle 1 Day 1
Plasma Concentration-time Profile (Tmax) of MEK162 (Phase Ib)
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Measured: Cycle 1 Day 1
Plasma Concentration-time Profile (Tmax,ss) of LEE011 (Phase Ib)
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Measured: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (Tmax,ss) of MEK162 (Phase Ib)
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Measured: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of LEE011 (Phase Ib)
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Measured: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of MEK162 (Phase Ib)
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Measured: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (T1/2,ss) of LEE011 (Phase Ib)
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Measured: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (T1/2,ss) of MEK162 (Phase Ib)
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Measured: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (CL/F) of LEE011 (Phase Ib)
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Measured: Cycle 1 Day 1
Plasma Concentration-time Profile (CL/F) of MEK162 (Phase Ib)
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Measured: Cycle 1 Day 1
Number of Participants With Adverse Drug Reactions
Safety and tolerability will be characterized through the incidence and severity of adverse drug reactions, serious adverse drug reactions, changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, dose reduction and dose intensity.
Measured: Approximately 12 months after FPFV
Duration of Response (DoR) - Phase 2
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
Please note: As clinicaltrials.gov only allows numerical data entry, the value of 999 indicates "not estimable" for confidence interval.
Measured: Approximately 12 months after the FPFV
Time to Progression (TTP) - Phase 2
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
Measured: Approximately 12 months after the FPFV
Progression Free Survival (PFS) - Phase 1b and Phase 2
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
In the Phase 1b part, patients were combined for purposes of PFS analyses based on schedule received, since too few patients received any individual dose level to allow for valid PFS estimates within the respective dose levels. This is how the data were analyses and presented for the clinical study report.
Measured: Approximately 12 months after the FPFV
Overall Survival (OS) - Phase ll
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
Measured: Approximately 12 months after the FPFV
Best Overall Response (BOR) - Phase II
To assess clinical safety according to RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
Measured: Approximately 12 months after the FPFV
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2013 (estimated)
- Study startJun 2013
- Primary completion15 Jan 2018
- Study completion20 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced or Metastatic NRAS Mutant MelanomaStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01781572
- Sponsor's protocol ID
- CMEK162X2114
- Other IDs
- C4211005
- Status last verified
- Nov 2020
- First submitted
- 24 Jan 2013
- Last updated
- 7 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 35294522
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II, Multicenter, Open Label, Study of LEE011 in Combination With MEK162 in Adult Patients With NRAS Mutant Melanoma
- ClinicalTrials.gov ID
- NCT01781572
- Acronym / sponsor ID
- CMEK162X2114
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Jun 2013
- Primary completion
- 15 Jan 2018 (actual)
- Study completion
- 20 Feb 2018 (actual)
- First posted
- 1 Feb 2013 (estimated)
- Results
- Posted 12 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the phase Ib, the primary purpose is to establish the maximum tolerated dose (MTD)(s)/recommended phase ll dose (RP2D) and schedule of LEE011 and MEK162 orally administered combination. Once the MTD(s)/RP2D have been determined for each tested schedule, additional patients will be enrolled in the phase II portion of the study at the RP2D on the chosen schedule in order to assess the anti-tumor activity of the combination in addition to continued evaluation of safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase Ib | Experimental | Drug: LEE011, Drug: MEK162The 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). |
| Phase II | Experimental | Drug: LEE011, Drug: MEK162The 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
- 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
Key exclusion criteria (21 listed)
- Presence of any brain metastases detected by MRI or CT with i.v. contrast of the brain at screening.
- Uncontrolled arterial hypertension despite medical treatment
- Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LEE011LEE011 will be administered orally once daily | Drug | Phase II, Phase Ib |
| MEK162MEK162 will be administered orally twice daily | Drug | Phase II, Phase Ib |
Primary outcome
Number of Dose Limiting Toxicities (Phase Ib)
Time frame: first 28 days of treatment
To estimate the maximum tolerate doses (MTDs) and/or identify the RP2D and schedule of LEE011 and MEK162 combination. A dose-limiting toxicity (DLT) was defined as an AE or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first cycle of treatment with ribociclib and binimetinib.
Objective Response Rate (ORR) (Phase II)
Time frame: Approximately 12 months after the FPFV
ORR is the proportion of patients with best overall response of complete response (CR) or partial response (PR) by month 2 assessed according to RECIST 1.1 criteria. ORR is done to describe the anti-tumor activity of LEE011 and MEK162 combination. The primary analysis of the ORR was based on the Investigator's assessment of overall lesion responses per RECIST 1.1.
26 secondary outcomes
Plasma Concentration-time Profile (AUCtau) of LEE011 (Phase Ib)
Time frame: Cycle 1 Day 1
Plasma Concentration-time Profile (AUCtau) of MEK162 (Phase Ib)
Time frame: Cycle 1 Day 1
Plasma Concentration-time Profile (AUCtau,ss) of LEE011 (Phase Ib)
Time frame: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (AUCtau,ss) of MEK162 (Phase Ib)
Time frame: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (Cmin,ss) of LEE011 (Phase Ib)
Time frame: For the 28-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 14
Plasma Concentration-time Profile (Cmin,ss) of MEK162 (Phase Ib)
Time frame: For the 28-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 14
Plasma Concentration-time Profile (Cmax) of LEE011 (Phase Ib)
Time frame: Cycle 1 Day 1
Plasma Concentration-time Profile (Cmax) of MEK162 (Phase Ib)
Time frame: Cycle 1 Day 1
Plasma Concentration-time Profile (Cmax,ss) of LEE011 (Phase Ib)
Time frame: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (Cmax,ss) of MEK162 (Phase Ib)
Time frame: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (Tmax) of LEE011 (Phase Ib)
Time frame: Cycle 1 Day 1
Plasma Concentration-time Profile (Tmax) of MEK162 (Phase Ib)
Time frame: Cycle 1 Day 1
Plasma Concentration-time Profile (Tmax,ss) of LEE011 (Phase Ib)
Time frame: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (Tmax,ss) of MEK162 (Phase Ib)
Time frame: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of LEE011 (Phase Ib)
Time frame: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of MEK162 (Phase Ib)
Time frame: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (T1/2,ss) of LEE011 (Phase Ib)
Time frame: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (T1/2,ss) of MEK162 (Phase Ib)
Time frame: For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
Plasma Concentration-time Profile (CL/F) of LEE011 (Phase Ib)
Time frame: Cycle 1 Day 1
Plasma Concentration-time Profile (CL/F) of MEK162 (Phase Ib)
Time frame: Cycle 1 Day 1
Number of Participants With Adverse Drug Reactions
Time frame: Approximately 12 months after FPFV
Duration of Response (DoR) - Phase 2
Time frame: Approximately 12 months after the FPFV
Time to Progression (TTP) - Phase 2
Time frame: Approximately 12 months after the FPFV
Progression Free Survival (PFS) - Phase 1b and Phase 2
Time frame: Approximately 12 months after the FPFV
Overall Survival (OS) - Phase ll
Time frame: Approximately 12 months after the FPFV
Best Overall Response (BOR) - Phase II
Time frame: Approximately 12 months after the FPFV
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35294522Schuler 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
17 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing LEE011 and MEK162 in people with Locally Advanced or Metastatic NRAS Mutant Melanoma, run by Pfizer at 17 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Germany, Australia, Netherlands, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Dose Limiting Toxicities (Phase Ib) (time frame: first 28 days of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01781572, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2020.