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

NCT ID: NCT01562899

Last Updated: 2020-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

77 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-08-27

Study Completion Date

2015-04-01

Brief Summary

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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.

Detailed Description

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Conditions

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Metastatic Pancreatic Adenocarcinoma BRAF Mutated Melanoma

Keywords

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MEK162 AMG 479 Ganitumab colorectal adenocarcinoma pancreatic adenocarcinoma melanoma KRAS BRAF

Study Design

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Allocation Method

NON_RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose escalation

Dose 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.

Group Type EXPERIMENTAL

MEK162

Intervention Type DRUG

Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure.

AMG 479

Intervention Type DRUG

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.

KRAS mutated colorectal adenocarcinoma

Patients 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.

Group Type EXPERIMENTAL

MEK162

Intervention Type DRUG

Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure.

AMG 479

Intervention Type DRUG

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.

Metastatic pancreatic adenocarcinoma

Patients 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.

Group Type EXPERIMENTAL

MEK162

Intervention Type DRUG

Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure.

AMG 479

Intervention Type DRUG

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.

BRAF mutated melanoma

Patients 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.

Group Type EXPERIMENTAL

MEK162

Intervention Type DRUG

Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure.

AMG 479

Intervention Type DRUG

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.

Interventions

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MEK162

Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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Binimetinib Ganitumab

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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Massachusetts General Hospital Mass General 2

Boston, Massachusetts, United States

Site Status

University of Utah / Huntsman Cancer Institute Huntsman

Salt Lake City, Utah, United States

Site Status

Pfizer Investigative Site

Parkville, Victoria, Australia

Site Status

Pfizer Investigative Site

Leuven, , Belgium

Site Status

Pfizer Investigative Site

Toronto, Ontario, Canada

Site Status

Pfizer Investigative Site

Toulouse, , France

Site Status

Pfizer Investigative Site

Napoli, , Italy

Site Status

Pfizer Investigative Site

Barcelona, Catalonia, Spain

Site Status

Pfizer Investigative Site

Sutton, Surrey, United Kingdom

Site Status

Countries

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Germany United States Australia Belgium Canada France Italy Spain United Kingdom

Other Identifiers

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C4211010

Identifier Type: OTHER

Identifier Source: secondary_id

2012-000305-76

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CMEK162X2111

Identifier Type: -

Identifier Source: org_study_id