A Study of MEK162 and AMG 479 in Patients With Selected Solid Tumors
This study is currently recruiting participants.
Verified February 2013 by Novartis
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01562899
First received: March 22, 2012
Last updated: February 25, 2013
Last verified: February 2013
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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. Patients who have not progressed at the time of discontinuation of study treatment should be radiologically followed for the disease status and phase II patients will be followed for survival.
| 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
| Estimated Enrollment: | 92 |
| 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01562899
Contacts
| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | |
| Contact: Novartis Pharmaceuticals |
Locations
| United States, Massachusetts | |
| Massachusetts General Hospital Mass General 2 | Recruiting |
| Boston, Massachusetts, United States, 02114 | |
| Contact 617-724-4000 | |
| Principal Investigator: Dejan Juric | |
| United States, Utah | |
| University of Utah / Huntsman Cancer Institute Huntsman | Recruiting |
| Salt Lake City, Utah, United States, 84103 | |
| Contact: Marlene Mitchell 801-587-4779 marlene.mitchell@hci.utah.edu | |
| Principal Investigator: Sunil Sharma | |
| Australia, Victoria | |
| Novartis Investigative Site | Recruiting |
| Parkville, Victoria, Australia, 3050 | |
| Belgium | |
| Novartis Investigative Site | Recruiting |
| Leuven, Belgium, 3000 | |
| Canada, Ontario | |
| Novartis Investigative Site | Recruiting |
| Toronto, Ontario, Canada, M5G 2M9 | |
| France | |
| Novartis Investigative Site | Recruiting |
| Toulouse Cedex 3, France, 31052 | |
| Italy | |
| Novartis Investigative Site | Recruiting |
| Napoli, Italy, 80131 | |
| Spain | |
| Novartis Investigative Site | Recruiting |
| Barcelona, Cataluna, Spain, 08035 | |
| United Kingdom | |
| Novartis Investigative Site | Recruiting |
| 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: | February 25, 2013 |
| Health Authority: | United States: Food and Drug Administration Australia: Therapeutic Goods Administration (TGA) Belgium: Federal Agency for Medicines and Health Products 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 Adenocarcinoma, Mucinous Melanoma Colorectal Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Cystic, Mucinous, and Serous Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal |
Neoplasms, Nerve Tissue Nevi and Melanomas Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases |
ClinicalTrials.gov processed this record on May 16, 2013