Study Stopped
Study was withdrawn due to scientific and business considerations.
A Study of MEK162 and AMG 479 in Patients With Selected Solid Tumors
A Phase Ib/II Open-label, Multi-center Study of the Combination of MEK162 Plus AMG 479 (Ganitumab) in Adult Patients With Selected Advanced Solid Tumors
3 other identifiers
interventional
77
8 countries
9
Brief Summary
This is a multi-center, open-label, phase Ib/II study. First, the aim of the phase Ib part is to estimate the MTD(s) and/or to identify the recommended phase II dose(s) (RP2D) for the combination of MEK162 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. The dose escalation part of the study will be guided by a Bayesian Logistic Regression Model (BLRM). At least 18 patients are expected to be enrolled in the dose escalation part. Following MTD/ RP2D declaration, patients will be enrolled in three phase II arms to assess efficacy of the combination as well as to better understand the safety, tolerability, PK, antibody concentrations and PD of the combination at MTD/RP2D. Phase II arm 1 will consist of approximately 25 patients with KRAS-mutant colorectal adenocarcinoma. Phase II arm 2 will consist of approximately 20 patients with metastatic pancreatic adenocarcinoma. Phase II arm 3 will consist of approximately 28 patients with mutant BRAFV600 melanoma. Patients will be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurs first. All patients will be followed up - at minimum patients must complete the safety follow-up assessments 30 days after the last dose of the study treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Aug 2012
Typical duration for phase_1
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 22, 2012
CompletedFirst Posted
Study publicly available on registry
March 26, 2012
CompletedStudy Start
First participant enrolled
August 27, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2015
CompletedDecember 10, 2020
December 1, 2020
2.6 years
March 22, 2012
December 9, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Phase Ib: Estimation of Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) by measuring incidence of dose limiting toxicities
To estimate the MTDs and/or RP2Ds of MEK162 in combination with AMG479 by measuring incidence of dose limiting toxicities in Cycle 1 (Cycle 1 = 28 days)
Approximately 6 months
Phase II: Antitumor activity of MEK162 in combination with AMG 479 by evaluating Objective Response Rate (ORR) in colorectal carcinoma and melanoma and by evaluating Disease Control Rate (DCR) at week 10 in pancreatic carcinoma
To estimate the antitumor activity of MEK162 in combination with AMG479 by evaluating Objective Response Rate (ORR) according to RECIST 1.1 in colorectal carcinoma and melanoma and by evaluating the Disease Control Rate (DCR) per RECIST 1.1 at week 10 in pancreatic carcinoma
Approximately 24 months
Secondary Outcomes (4)
Both Phases: Safety and tolerability of MEK162 & AMG 479 (ganitumab) in combination by evaluating the adverse events, serious adverse events, changes in hematology and chemistry values, vital signs, ECGs; dose interruptions, reductions and dose intensity
Phase Ib: Approximately 6 months; Phase II: Approximately 24 months
Both Phases: Determination of single and multiple dose pharmacokinetics (PK) profile of MEK162 in combination with AMG 479 (ganitumab) by measuring time vs. plasma concentrations and basic PK parameters of MEK162
Phase Ib: Approximately 6 months; Phase II: Approximately 24 months
Phase Ib: Preliminary anti-tumor activity of MEK162 and AMG 479 (ganitumab) in combination by evaluating the Overall Response Rate (ORR), Duration of Response (DOR) and Progression Free Survival (PFS)
Approximately 6 months
Phase II: Further anti-tumor activity of MEK162 & AMG 479 (ganitumab) in combination by evaluating the DOR, PFS and OS by evaluating Disease Control Rate for colorectal carcinoma and melanoma; Overall Response Rate for pancreatic carcinoma patients
Approximately 24 months
Study Arms (4)
Dose escalation
EXPERIMENTALDose finding group chosen in order to establish a safe and tolerated dose of binimetinib in combination with ganitumab in patients with selected advanced solid tumors.
KRAS mutated colorectal adenocarcinoma
EXPERIMENTALPatients with KRAS mutant colorectal cancer. The starting dose (30 mg bid) of binimetinib chosen for this study was a fraction of the MTD (60 mg bid) and the RP2D (45 mg bid) determined for single agent use. The starting dose for ganitumab was 12 mg/kg q2w which had been shown to be a well-tolerated dose in combination with other anti-cancer agents.
Metastatic pancreatic adenocarcinoma
EXPERIMENTALPatients with metastatic pancreatic cancer. The starting dose (30 mg bid) of binimetinib chosen for this study was a fraction of the MTD (60 mg bid) and the RP2D (45 mg bid) determined for single agent use. The starting dose for ganitumab was 12 mg/kg q2w which had been shown to be a well-tolerated dose in combination with other anti-cancer agents.
BRAF mutated melanoma
EXPERIMENTALPatients with mutant BRAF V600 melanoma. The starting dose (30 mg bid) of binimetinib chosen for this study was a fraction of the MTD (60 mg bid) and the RP2D (45 mg bid) determined for single agent use. The starting dose for ganitumab was 12 mg/kg q2w which had been shown to be a well-tolerated dose in combination with other anti-cancer agents.
Interventions
Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure.
Supplied as sterile liquid for intravenous infusion in vials in boxes. Until April 2013 a frozen formulation with a concentration of 30 mg/ml was used; from May 2013 onwards a refrigerated formulation with a concentration of 70 mg/ml was used.
Eligibility Criteria
You may qualify if:
- Patients aged ≥ 18 years
- Patients with advanced solid tumors (CRC, melanoma) with documented somatic KRAS or BRAFV600 mutations in tumor tissue. Patients with metastatic pancreatic adenocarcinoma may be enrolled irrespectively of KRAS or BRAFV600 mutational status.
- Patients must have relapsed or progressed following standard therapy or patients for whom no standard anticancer therapy exists.
- Measurable disease as determined by RECIST v1.1. World Health Organization (WHO) Performance Status (PS) ≤ 2.
- Adequate organ function
- Negative serum pregnancy test
You may not qualify if:
- Prior therapy with MEK- or IGF-1R- inhibitor
- History or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or retinal degenerative disease
- Patients with known history of severe infusion reactions to monoclonal antibodies
- Patients with primary CNS tumor or CNS tumor involvement
- History of thromboembolic event requiring full-dose anticoagulation therapy
- Clinically significant cardiac disease
- History of another malignancy within 2 years
- Pregnant or nursing (lactating) women
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (9)
Massachusetts General Hospital Mass General 2
Boston, Massachusetts, 02114, United States
University of Utah / Huntsman Cancer Institute Huntsman
Salt Lake City, Utah, 84103, United States
Pfizer Investigative Site
Parkville, Victoria, 3050, Australia
Pfizer Investigative Site
Leuven, 3000, Belgium
Pfizer Investigative Site
Toronto, Ontario, M5G 2M9, Canada
Pfizer Investigative Site
Toulouse, 31059, France
Pfizer Investigative Site
Napoli, 80131, Italy
Pfizer Investigative Site
Barcelona, Catalonia, 08035, Spain
Pfizer Investigative Site
Sutton, Surrey, SM2 5PT, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 22, 2012
First Posted
March 26, 2012
Study Start
August 27, 2012
Primary Completion
April 1, 2015
Study Completion
April 1, 2015
Last Updated
December 10, 2020
Record last verified: 2020-12
Data Sharing
- IPD Sharing
- Will share
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.