A Study of MEK162 and AMG 479 in Patients With Selected Solid Tumors

Metastatic Pancreatic Adenocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01562899
• Other study ID #: CMEK162X2111
• Secondary ID: C42110102012-000
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: August 27, 2012
• Est. completion date: April 1, 2015

Study information

• Verified date: December 2020
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 77
• Est. completion date: April 1, 2015
• Est. primary completion date: April 1, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• BRAF Mutated Melanoma
• Melanoma
• Metastatic Pancreatic Adenocarcinoma

Intervention

Drug:
• MEK162
Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure.
• AMG 479
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.

Locations

Country	Name	City	State
Australia	Pfizer Investigative Site	Parkville	Victoria
Belgium	Pfizer Investigative Site	Leuven
Canada	Pfizer Investigative Site	Toronto	Ontario
France	Pfizer Investigative Site	Toulouse Cedex 9
Italy	Pfizer Investigative Site	Napoli
Spain	Pfizer Investigative Site	Barcelona	Catalunya
United Kingdom	Pfizer Investigative Site	Sutton	Surrey
United States	Massachusetts General Hospital Mass General 2	Boston	Massachusetts
United States	University of Utah / Huntsman Cancer Institute Huntsman	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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	To characterize the safety and tolerability of MEK162 and AMG 479 (ganitumab) in combination by evaluating the incidence and severity of adverse events, serious adverse events (as per CTCAE grading), 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
Secondary	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	To determine single and multiple dose PK profile of MEK162 in combination with AMG 479 (ganitumab) by measuring time vs. plasma concentration as well as basic PK parameters of MEK162 at different timepoints prior and post study drug combination dosing.	Phase Ib: Approximately 6 months; Phase II: Approximately 24 months
Secondary	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)	To assess preliminary anti-tumor activity of MEK162 and AMG 479 (ganitumab) in combination by evaluating Overall Response Rate (ORR), Duration of Response (DOR), Progression Free Survival (PFS) as assessed by the investigator according to RECIST 1.1	Approximately 6 months
Secondary	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	To further assess the anti-tumor activity of MEK162 and AMG 479 (ganitumab) in combination by evaluating the Duration of Response (DOR) and Progression Free Survival (PFS) per RECIST 1.1 and Overall Survival in all phase II patients and by evaluating the Disease Control Rate (DCR) per RECIST 1.1 for colorectal carcinoma and melanoma and Overall Response Rate (ORR) per RECIST 1.1 for pancreatic carcinoma patients	Approximately 24 months