A Phase 1b/2a Study Evaluating AMG 232 in Metastatic Melanoma

• ClinicalTrials.gov Identifier: NCT02110355
• Recruitment Status: Completed
• First Posted: April 10, 2014
• Last Update Posted: October 8, 2019
• Sponsor: Amgen
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): Amgen

Study Description

Brief Summary:

Phase 1b/2a, open-label, sequential dose escalation and expansion study of AMG 232 in combination with trametinib and dabrafenib in subjects with metastatic melanoma followed by a direct comparison of AMG 232 combined with trametinib and dabrafenib versus trametinib combined with dabrafenib alone.

Condition or disease	Intervention/treatment	Phase
Advanced Malignancy; Advanced Solid Tumors; Cancer; Oncology; Oncology Patients; Tumors; Melanoma	Drug: AMG 232; Drug: Trametinib; Drug: Dabrafenib	Phase 1; Phase 2

Detailed Description:

The study will be conducted in 3 parts: Part 1 - Dose Escalation, Part 2 - Dose Expansion and Part 3, a randomized Phase 2a.

In both part 1 and 2, subjects will be enrolled open-label into 1 of 2 arms. For both Arm 1 and Arm 2, the part 1 dose escalation is aimed at determining an AMG 232 maximum tolerated dose (MTD) with a fixed dose of the combination drug(s) and evaluating safety, tolerability, pharmacokinetics and pharmacodynamics of each combination. Part 2 dose expansion will enroll subjects to receive therapy with a dose and schedule of AMG 232 selected from the corresponding part 1 dose escalation. In part 2 subjects will be enrolled to confirm safety and tolerability and to assess clinical activity prior to proceeding to Part 3, Phase 2a. In Phase 2a, Subjects will be randomized open-label in a 1:1 ratio to receive AMG 232 in combination with trametinib plus dabrafenib versus trametinib plus dabrafenib alone.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b/2a Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of AMG 232 Combined With Trametinib and Dabrafenib or Trametinib in Adult Subjects With Metastatic Cutaneous Melanoma
• Actual Study Start Date: December 19, 2014
• Actual Primary Completion Date: December 27, 2018
• Actual Study Completion Date: December 27, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: AMG 232 with Trametinib and Dabrabenib; Arm 1 of Part 1 and 2 and Part 3	Drug: AMG 232; Given as an oral tablet in escalating doses; Drug: Trametinib; Trametinib is an anti-cancer agent; Drug: Dabrafenib; Dabrafenib is an anti-cancer agent
Experimental: AMG 232 with Trametinib; Arm 2 of Part 1 and 2	Drug: AMG 232; Given as an oral tablet in escalating doses; Drug: Trametinib; Trametinib is an anti-cancer agent
Active Comparator: Trametinib and Dabrafenib; Part 3	Drug: Trametinib; Trametinib is an anti-cancer agent; Drug: Dabrafenib; Dabrafenib is an anti-cancer agent

Outcome Measures

Primary Outcome Measures :

1. Subject incidence of treatment-emergent adverse events, Results of safety laboratory tests, vital sign measurements, ECG measurements, PK parameters; Progression-free Survival Rate [ Time Frame: 36 months ]
   Incidence and grade of treatment-emergent adverse events, including dose-limiting toxicities; AMG 232, trametinib, dabrafenib, and metabolite PK parameters; progression-free Survival

Secondary Outcome Measures :

1. Time to and duration of overall response and duration of stable disease measured by CT or MRI and assessed per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, Progression-free and Overall Survival [ Time Frame: 36 months ]
   Objective Tumor Response

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria: Subjects must have histologically or cytologically confirmed metastatic cutaneous or mucosal melanoma, Able to swallow and retain orally administered medication, Adequate hematological, renal, hepatic, and coagulation laboratory assessments Exclusion Criteria: Clinically significant bleeding within 4 weeks of screening, Current use of warfarin, factor Xa inhibitors, and direct thrombin inhibitors, Infection requiring anti-infective treatments within 1 week of study enrollment, Anti-tumor therapy, Major surgery within 28 days

Contacts and Locations

Locations

United States, California

Research Site

Los Angeles, California, United States, 90095

United States, Colorado

Research Site

Aurora, Colorado, United States, 80045

United States, Massachusetts

Research Site

Boston, Massachusetts, United States, 02114

United States, North Carolina

Research Site

Chapel Hill, North Carolina, United States, 27599

United States, Tennessee

Research Site

Nashville, Tennessee, United States, 37232

Australia, New South Wales

Research Site

North Sydney, New South Wales, Australia, 2060

Australia, Victoria

Research Site

Melbourne, Victoria, Australia, 3000

Sponsors and Collaborators

Amgen

GlaxoSmithKline

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02110355
• Other Study ID Numbers: 20120238
• First Posted: April 10, 2014
• Last Update Posted: October 8, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• URL: https://www.amgen.com/datasharing

Keywords provided by Amgen:

Metastatic melanoma

Additional relevant MeSH terms:

Melanoma; Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Trametinib; Dabrafenib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action