Clinical trial NCT01927341: Phase Ib/II Study of Efficacy and Safety of MEK162 and Panitumumab, in Adult mCRC Patients With Mutant or Wild-type RAS Tumors
Official title: A Phase Ib/II, Open-label, Multi-center, Dose Escalation Study of MEK162 in Combination With Panitumumab in Adult Patients With Mutant RAS or Wild-type RAS Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: MEK162,
panitumumab,
mutant RAS,
wild-type RAS,
metastatic colorectal cancer,
adult mCRC patient
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-08-22
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The primary purpose of the phase Ib is to estimate the MTD/RPD2 and of the phase II is to assess the anti-tumor activity of MEK162 in combination with panitumumab.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Metastatic colorectal cancer
* Progression on or following standard therapy, or no standard therapy (phase Ib). Progression on or following at least 2-prior fluoropyrimidine-containing chemotherapy regimens (phase II)
* Written documentation of mutant or wild-type RAS
* Life expectancy ≥ 3 months
* ECOG performance status ≤ 2

Exclusion Criteria:

Phase II arms 1 and 4 only: previous treatment with cetuximab, panitumumab, and/or other EGFR inhibitors

* Previous treatment with MEK-inhibitors
* History of severe infusion reactions to monoclonal antibodies.
* Symptomatic or untreated leptomeningeal disease
* Symptomatic brain metastasis
* Current evidence of retinal disease; history of CSR, RVO or ophthalmopathy as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO and history of keratitis.
* Acute or chronic pancreatitis
* Clinically significant cardiac disease
* Not adequate hematologic, renal and hepatic function

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLT): Phase 1b
timeFrame: Within the first 28 days of treatment with binimetinib and panitumumab (Cycle 1)
measure: Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 2
timeFrame: From the start of the treatment until CR or PR (approximately up to 11 months)
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE)
timeFrame: Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)
measure: Number of Participants With Vital Sign Abnormalities
timeFrame: Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities
timeFrame: Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)
measure: Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 1b
timeFrame: From the start of the treatment until disease progression (approximately up to 11 months)
measure: Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment
timeFrame: From the date of randomization to the date of the first documented PD or death (approximately up to 11 months)
measure: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment
timeFrame: From the first documented occurrence of response (PR or CR) until the date of the first documented PD or death due to the underlying cancer (approximately up to 11 months)
measure: Disease Control Rate (DCR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment
timeFrame: From the start of the treatment until disease progression (approximately up to 11 months)
measure: Overall Survival (OS)
timeFrame: From the start of treatment to the date of death due to any cause (approximately up to 11 months)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California at Los Angeles Dept of Onc
state: California
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Oncology Dept
state: New York
city: Leuven
country: Belgium
facility: Pfizer Investigative Site
city: Toronto
country: Canada
facility: Pfizer Investigative Site
state: Ontario
city: Toulouse Cedex 9
country: France
facility: Pfizer Investigative Site
city: Milano
country: Italy
facility: Pfizer Investigative Site
state: MI
city: Amsterdam
country: Netherlands
facility: Pfizer Investigative Site
city: Barcelona
country: Spain
facility: Pfizer Investigative Site
state: Catalunya
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: