Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01781572
Registration number
NCT01781572
Ethics application status
Date submitted
24/01/2013
Date registered
1/02/2013
Date last updated
7/12/2020
Titles & IDs
Public title
A Phase Ib/II Study of LEE011 in Combination With MEK162 in Patients With NRAS Mutant Melanoma
Query!
Scientific title
A Phase Ib/II, Multicenter, Open Label, Study of LEE011 in Combination With MEK162 in Adult Patients With NRAS Mutant Melanoma
Query!
Secondary ID [1]
0
0
C4211005
Query!
Secondary ID [2]
0
0
CMEK162X2114
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Locally Advanced or Metastatic NRAS Mutant Melanoma
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Malignant melanoma
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - LEE011
Treatment: Drugs - MEK162
Experimental: 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).
Experimental: 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.
Treatment: Drugs: LEE011
LEE011 will be administered orally once daily
Treatment: Drugs: MEK162
MEK162 will be administered orally twice daily
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Number of Dose Limiting Toxicities (Phase Ib)
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
first 28 days of treatment
Query!
Primary outcome [2]
0
0
Objective Response Rate (ORR) (Phase II)
Query!
Assessment method [2]
0
0
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.
Query!
Timepoint [2]
0
0
Approximately 12 months after the FPFV
Query!
Secondary outcome [1]
0
0
Plasma Concentration-time Profile (AUCtau) of LEE011 (Phase Ib)
Query!
Assessment method [1]
0
0
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [1]
0
0
Cycle 1 Day 1
Query!
Secondary outcome [2]
0
0
Plasma Concentration-time Profile (AUCtau) of MEK162 (Phase Ib)
Query!
Assessment method [2]
0
0
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [2]
0
0
Cycle 1 Day 1
Query!
Secondary outcome [3]
0
0
Plasma Concentration-time Profile (AUCtau,ss) of LEE011 (Phase Ib)
Query!
Assessment method [3]
0
0
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [3]
0
0
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
Query!
Secondary outcome [4]
0
0
Plasma Concentration-time Profile (AUCtau,ss) of MEK162 (Phase Ib)
Query!
Assessment method [4]
0
0
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [4]
0
0
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
Query!
Secondary outcome [5]
0
0
Plasma Concentration-time Profile (Cmin,ss) of LEE011 (Phase Ib)
Query!
Assessment method [5]
0
0
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [5]
0
0
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
Query!
Secondary outcome [6]
0
0
Plasma Concentration-time Profile (Cmin,ss) of MEK162 (Phase Ib)
Query!
Assessment method [6]
0
0
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [6]
0
0
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
Query!
Secondary outcome [7]
0
0
Plasma Concentration-time Profile (Cmax) of LEE011 (Phase Ib)
Query!
Assessment method [7]
0
0
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [7]
0
0
Cycle 1 Day 1
Query!
Secondary outcome [8]
0
0
Plasma Concentration-time Profile (Cmax) of MEK162 (Phase Ib)
Query!
Assessment method [8]
0
0
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [8]
0
0
Cycle 1 Day 1
Query!
Secondary outcome [9]
0
0
Plasma Concentration-time Profile (Cmax,ss) of LEE011 (Phase Ib)
Query!
Assessment method [9]
0
0
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [9]
0
0
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
Query!
Secondary outcome [10]
0
0
Plasma Concentration-time Profile (Cmax,ss) of MEK162 (Phase Ib)
Query!
Assessment method [10]
0
0
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [10]
0
0
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
Query!
Secondary outcome [11]
0
0
Plasma Concentration-time Profile (Tmax) of LEE011 (Phase Ib)
Query!
Assessment method [11]
0
0
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [11]
0
0
Cycle 1 Day 1
Query!
Secondary outcome [12]
0
0
Plasma Concentration-time Profile (Tmax) of MEK162 (Phase Ib)
Query!
Assessment method [12]
0
0
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [12]
0
0
Cycle 1 Day 1
Query!
Secondary outcome [13]
0
0
Plasma Concentration-time Profile (Tmax,ss) of LEE011 (Phase Ib)
Query!
Assessment method [13]
0
0
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [13]
0
0
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
Query!
Secondary outcome [14]
0
0
Plasma Concentration-time Profile (Tmax,ss) of MEK162 (Phase Ib)
Query!
Assessment method [14]
0
0
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [14]
0
0
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
Query!
Secondary outcome [15]
0
0
Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of LEE011 (Phase Ib)
Query!
Assessment method [15]
0
0
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [15]
0
0
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
Query!
Secondary outcome [16]
0
0
Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of MEK162 (Phase Ib)
Query!
Assessment method [16]
0
0
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [16]
0
0
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
Query!
Secondary outcome [17]
0
0
Plasma Concentration-time Profile (T1/2,ss) of LEE011 (Phase Ib)
Query!
Assessment method [17]
0
0
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [17]
0
0
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
Query!
Secondary outcome [18]
0
0
Plasma Concentration-time Profile (T1/2,ss) of MEK162 (Phase Ib)
Query!
Assessment method [18]
0
0
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [18]
0
0
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
Query!
Secondary outcome [19]
0
0
Plasma Concentration-time Profile (CL/F) of LEE011 (Phase Ib)
Query!
Assessment method [19]
0
0
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [19]
0
0
Cycle 1 Day 1
Query!
Secondary outcome [20]
0
0
Plasma Concentration-time Profile (CL/F) of MEK162 (Phase Ib)
Query!
Assessment method [20]
0
0
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
Query!
Timepoint [20]
0
0
Cycle 1 Day 1
Query!
Secondary outcome [21]
0
0
Number of Participants With Adverse Drug Reactions
Query!
Assessment method [21]
0
0
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.
Query!
Timepoint [21]
0
0
Approximately 12 months after FPFV
Query!
Secondary outcome [22]
0
0
Duration of Response (DoR) - Phase 2
Query!
Assessment method [22]
0
0
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.
Query!
Timepoint [22]
0
0
Approximately 12 months after the FPFV
Query!
Secondary outcome [23]
0
0
Time to Progression (TTP) - Phase 2
Query!
Assessment method [23]
0
0
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
Query!
Timepoint [23]
0
0
Approximately 12 months after the FPFV
Query!
Secondary outcome [24]
0
0
Progression Free Survival (PFS) - Phase 1b and Phase 2
Query!
Assessment method [24]
0
0
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.
Query!
Timepoint [24]
0
0
Approximately 12 months after the FPFV
Query!
Secondary outcome [25]
0
0
Overall Survival (OS) - Phase ll
Query!
Assessment method [25]
0
0
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
Query!
Timepoint [25]
0
0
Approximately 12 months after the FPFV
Query!
Secondary outcome [26]
0
0
Best Overall Response (BOR) - Phase II
Query!
Assessment method [26]
0
0
To assess clinical safety according to RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
Query!
Timepoint [26]
0
0
Approximately 12 months after the FPFV
Query!
Eligibility
Key inclusion criteria
- 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
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.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
- 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:
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).
Other protocol related inclusion/exclusion criteria may apply.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Single group
Query!
Other design features
Query!
Phase
Phase 1/Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/06/2013
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
20/02/2018
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
102
Query!
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Query!
Recruitment hospital [1]
0
0
Pfizer Investigative Site 1003 - North Sydney
Query!
Recruitment hospital [2]
0
0
Pfizer Investigative Site 1002 - Westmead
Query!
Recruitment hospital [3]
0
0
Pfizer Investigator Site 1001 - East Melbourne
Query!
Recruitment postcode(s) [1]
0
0
2060 - North Sydney
Query!
Recruitment postcode(s) [2]
0
0
2145 - Westmead
Query!
Recruitment postcode(s) [3]
0
0
- East Melbourne
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Michigan
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
New York
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Tennessee
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Texas
Query!
Country [6]
0
0
Germany
Query!
State/province [6]
0
0
Essen
Query!
Country [7]
0
0
Germany
Query!
State/province [7]
0
0
Gera
Query!
Country [8]
0
0
Germany
Query!
State/province [8]
0
0
Hannover
Query!
Country [9]
0
0
Germany
Query!
State/province [9]
0
0
Muenchen
Query!
Country [10]
0
0
Italy
Query!
State/province [10]
0
0
Napoli
Query!
Country [11]
0
0
Netherlands
Query!
State/province [11]
0
0
The Netherlands
Query!
Country [12]
0
0
Netherlands
Query!
State/province [12]
0
0
Nijmegen
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Pfizer
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief 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. 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.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT01781572
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Pfizer CT.gov Call Center
Query!
Address
0
0
Pfizer
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01781572
Download to PDF