Clinical trial NCT01562899: A Study of MEK162 and AMG 479 in Patients With Selected Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Metastatic Pancreatic Adenocarcinoma
BRAF Mutated Melanoma
Keywords: MEK162
AMG 479
Ganitumab
colorectal adenocarcinoma
pancreatic adenocarcinoma
melanoma
KRAS
BRAF
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-03-26
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Phase Ib: Estimation of Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) by measuring incidence of dose limiting toxicities
timeFrame: Approximately 6 months
measure: 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
timeFrame: Approximately 24 months
Secondary outcomes:
measure: 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
timeFrame: Phase Ib: Approximately 6 months; Phase II: Approximately 24 months
measure: 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
timeFrame: Phase Ib: Approximately 6 months; Phase II: Approximately 24 months
measure: 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)
timeFrame: Approximately 6 months
measure: 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
timeFrame: Approximately 24 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital Mass General 2
state: Massachusetts
city: Salt Lake City
country: United States
facility: University of Utah / Huntsman Cancer Institute Huntsman
state: Utah
city: Parkville
country: Australia
facility: Pfizer Investigative Site
state: Victoria
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: Napoli
country: Italy
facility: Pfizer Investigative Site
city: Barcelona
country: Spain
facility: Pfizer Investigative Site
state: Catalunya
city: Sutton
country: United Kingdom
facility: Pfizer Investigative Site
state: Surrey
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: