January 24, 2013
|
February 1, 2013
|
May 6, 2020
|
August 12, 2020
|
December 7, 2020
|
June 2013
|
January 15, 2018 (Final data collection date for primary outcome measure)
|
- 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.
|
- Incidence 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.
- Objective response rate (ORR) (phase II) [ Time Frame: Baseline, every 2-4 months ]
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.
|
|
- Plasma Concentration-time Profile (AUCtau) of LEE011 (Phase Ib) [ Time Frame: Cycle 1 Day 1 ]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (AUCtau) of MEK162 (Phase Ib) [ Time Frame: Cycle 1 Day 1 ]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- 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 ]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- 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 ]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- 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 ]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- 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 ]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Cmax) of LEE011 (Phase Ib) [ Time Frame: Cycle 1 Day 1 ]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Cmax) of MEK162 (Phase Ib) [ Time Frame: Cycle 1 Day 1 ]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- 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 ]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- 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 ]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Tmax) of LEE011 (Phase Ib) [ Time Frame: Cycle 1 Day 1 ]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Tmax) of MEK162 (Phase Ib) [ Time Frame: Cycle 1 Day 1 ]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- 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 ]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- 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 ]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- 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 ]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- 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 ]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- 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 ]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- 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 ]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (CL/F) of LEE011 (Phase Ib) [ Time Frame: Cycle 1 Day 1 ]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (CL/F) of MEK162 (Phase Ib) [ Time Frame: Cycle 1 Day 1 ]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- Number of Participants With Adverse Drug Reactions [ Time Frame: Approximately 12 months after FPFV ]
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.
- Duration of Response (DoR) - Phase 2 [ Time Frame: Approximately 12 months after the FPFV ]
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.
- Time to Progression (TTP) - Phase 2 [ Time Frame: Approximately 12 months after the FPFV ]
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
- Progression Free Survival (PFS) - Phase 1b and Phase 2 [ Time Frame: Approximately 12 months after the FPFV ]
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.
- Overall Survival (OS) - Phase ll [ Time Frame: Approximately 12 months after the FPFV ]
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
- Best Overall Response (BOR) - Phase II [ Time Frame: Approximately 12 months after the FPFV ]
To assess clinical safety according to RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
|
- Plasma concentration-time profile (AUCtau) of LEE011 and MEK162 (phase Ib) [ Time Frame: up to 24 weeks ]
To Characterize the PK profiles of LEE011 and MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma concentration-time profile (AUCtau,ss) of LEE011 and MEK162 (phase Ib) [ Time Frame: up to 24 weeks ]
To Characterize the PK profiles of LEE011 and MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma concentration-time profile (Cmin,ss) of LEE011 and MEK162 (phase Ib) [ Time Frame: up to 24 weeks ]
To Characterize the PK profiles of LEE011 and MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma concentration-time profiles of LEE011 and MEK162 (phase Ib) [ Time Frame: up to 24 weeks ]
Evaluation of PK parameters, including but not limited to AUCtau, AUCtau,ss, Cmin,ss, Cmax, Cmax,ss ,Tmax, Tmax,ss, accumulation ratio (Racc), and T1/2,acc, CL/F in cycle 1-6. (Phase Ib).
- Plasma concentration-time profile (Cmax) of LEE011 and MEK162 (phase Ib) [ Time Frame: up to 24 weeks ]
To Characterize the PK profiles of LEE011 and MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma concentration-time profile (Cmax,ss) of LEE011 and MEK162 (phase Ib) [ Time Frame: up to 24 weeks ]
To Characterize the PK profiles of LEE011 and MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma concentration-time profile (Tmax) of LEE011 and MEK162 (phase Ib) [ Time Frame: up to 24 weeks ]
To Characterize the PK profiles of LEE011 and MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma concentration-time profile (Tmax,ss) of LEE011 and MEK162 (phase Ib) [ Time Frame: up to 24 weeks ]
To Characterize the PK profiles of LEE011 and MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma concentration-time profile (accumulation ration, Racc) of LEE011 and MEK162 (phase Ib) [ Time Frame: up to 24 weeks ]
To Characterize the PK profiles of LEE011 and MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma concentration-time profile (T1/2, acc) of LEE011 and MEK162 (phase Ib) [ Time Frame: up to 24 weeks ]
To Characterize the PK profiles of LEE011 and MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma concentration-time profile (CL/F) of LEE011 and MEK162 (phase Ib) [ Time Frame: up to 24 weeks ]
To Characterize the PK profiles of LEE011 and MEK162 as well as any other significant metabolites identified (Phase Ib).
- Incidence of adverse drug reactions [ Time Frame: Approximatley 12 months after FPFV ]
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.
- Duration of Response (DoR) - Phase ll [ Time Frame: Approximatley 12 months after the FPFV ]
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
- Time to Progression (TTP) - Phase ll [ Time Frame: Approximately 12 months after the FPFV ]
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
- Progression Free Survival (PFS) - Phase ll [ Time Frame: Approximatley 12 months after the FPFV ]
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
- Overall Survival (OS) - Phase ll [ Time Frame: Approximately 12 months after the FPFV ]
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
- Best Overall Response (BOR) - Phase ll [ Time Frame: Approximately 12 months after the FPFV ]
To assess clinical safety according to RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
|
Not Provided
|
Not Provided
|
|
A Phase Ib/II Study of LEE011 in Combination With MEK162 in Patients With NRAS Mutant Melanoma
|
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.
|
Not Provided
|
Interventional
|
Phase 1 Phase 2
|
Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
|
Locally Advanced or Metastatic NRAS Mutant Melanoma
|
|
- 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).
Interventions:
- Drug: LEE011
- Drug: MEK162
- 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.
Interventions:
- Drug: LEE011
- Drug: MEK162
|
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.
|
|
Completed
|
102
|
58
|
February 20, 2018
|
January 15, 2018 (Final data collection date for primary outcome measure)
|
Inclusion Criteria:
Exclusion Criteria:
Other protocol related inclusion/exclusion criteria may apply.
|
Sexes Eligible for Study: |
All |
|
18 Years and older (Adult, Older Adult)
|
No
|
Contact information is only displayed when the study is recruiting subjects
|
Australia, Germany, Italy, Netherlands, United States
|
Norway
|
|
NCT01781572
|
CMEK162X2114 C4211005 ( Other Identifier: Pfizer )
|
No
|
Not Provided
|
Not Provided
|
Pfizer
|
Novartis Pharmaceuticals
|
Pfizer
|
Novartis Pharmaceuticals
|
Not Provided
|
Study Director: |
Pfizer CT.gov Call Center |
Pfizer |
|
Pfizer
|
November 2020
|