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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01562899
First received: March 22, 2012
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
KRAS Mutated Colorectal Adenocarcinoma.
Metastatic Pancreatic Adenocarcinoma
BRAF Mutated Melanoma
Drug: MEK162 + AMG 479
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Phase Ib: Estimation of Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) by measuring incidence of dose limiting toxicities [ Time Frame: Approximately 6 months ] [ Designated as safety issue: Yes ]
    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)

  • 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 [ Time Frame: Approximately 24 months ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • 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 [ Time Frame: Phase Ib: Approximately 6 months; Phase II: Approximately 24 months ] [ Designated as safety issue: Yes ]
    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

  • 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 [ Time Frame: Phase Ib: Approximately 6 months; Phase II: Approximately 24 months ] [ Designated as safety issue: No ]
    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: 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) [ Time Frame: Approximately 6 months ] [ Designated as safety issue: No ]
    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

  • 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 [ Time Frame: Approximately 24 months ] [ Designated as safety issue: No ]
    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


Enrollment: 77
Study Start Date: August 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose escalation, Drug: MEK162 + AMG 479
Experimental: KRAS mutated colorectal adenocarcinoma, Drug: MEK162 + AMG 479
Experimental: metastatic pancreatic adenocarcinoma, Drug: MEK162 + AMG 479
Experimental: BRAF mutated melanoma Drug: MEK162 + AMG 479

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01562899

Locations
United States, Massachusetts
Massachusetts General Hospital Mass General 2
Boston, Massachusetts, United States, 02114
United States, Utah
University of Utah / Huntsman Cancer Institute Huntsman
Salt Lake City, Utah, United States, 84112
Australia, Victoria
Novartis Investigative Site
Parkville, Victoria, Australia, 3050
Belgium
Novartis Investigative Site
Leuven, Belgium, 3000
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
France
Novartis Investigative Site
Toulouse Cedex 3, France, 31052
Italy
Novartis Investigative Site
Napoli, Italy, 80131
Spain
Novartis Investigative Site
Barcelona, Cataluna, Spain, 08035
United Kingdom
Novartis Investigative Site
Sutton, Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01562899     History of Changes
Other Study ID Numbers: CMEK162X2111, 2012-000305-76
Study First Received: March 22, 2012
Last Updated: March 31, 2014
Health Authority: United States: Food and Drug Administration
Australia: Therapeutic Goods Administration (TGA)
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Canada: Health Canada
France: Agence française de sécurité sanitaire des produits de santé (Afssaps)
Italy: Agenzia Italiana del Farmaco
Germany: Paul-Ehrlich-Institute
Spain: Spanish Agency of Medicines and Health Products (AEMPS)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: The Italian Medicines Agency
Germany: Paul-Ehrlich-Institut
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Novartis:
MEK162
AMG 479
Ganitumab
colorectal adenocarcinoma
pancreatic adenocarcinoma
melanoma
KRAS
BRAF

Additional relevant MeSH terms:
Adenocarcinoma
Melanoma
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas

ClinicalTrials.gov processed this record on October 30, 2014