MEK162 and RAF265 in Adult Patients With Advanced Solid Tumors Harboring RAS or BRAFV600E Mutations

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01352273
First received: May 2, 2011
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

This is a multi- center, open-label, dose finding, Phase Ib study to be conducted in two stages: a dose escalation part to determine the maximum tolerated dose (MTD) safety and tolerability of concurrent administration of MEK162 and RAF265, followed by an expansion part to further assess the safety and preliminary anti-tumor efficacy of this oral combination within two separate patient populations: i) patients with advanced solid tumors harboring BRAFV600E mutations or ii) patients with advanced solid tumors harboring RAS mutations.


Condition Intervention Phase
Advanced Solid Tumors
Drug: MEK162 + RAF265
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib Open-label Dose Escalation Study of MEK162 and RAF265 in Adult Patients With Advanced Solid Tumors Harboring RAS or BRAFV600E Mutations

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence of Dose Limiting Toxicities [ Time Frame: during the first 28 days of treatment with RAF265 and MEK162 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of participants with adverse events and serious adverse events [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • assess preliminary anti-tumor activity of the combination [ Time Frame: every 8 weeks of treatment ] [ Designated as safety issue: Yes ]
    CT scan will be performed

  • Tumor skin and blood samples will be collected before and during treatment with RAF265 and MEK162 to assess the combination's effects on the RAF/MEK/MAPK pathway with the clinical outcomes [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Time versus plasma concentration profiles of RAF265 and MEK162 [ Time Frame: 10 months ] [ Designated as safety issue: No ]

Enrollment: 69
Study Start Date: June 2011
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MEK162 + RAF265 Drug: MEK162 + RAF265

  Eligibility

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

Inclusion Criteria:

Patients with histologically or cytologically confirmed and non-resectable advanced solid tumors for which no further effective standard therapy exists.

  • The patients' tumors must contain documented activating somatic BRAFV600E* , NRAS or KRAS mutations (except for pancreatic cancer)
  • All patients enrolled MUST provide fresh or archival tumor samples at baseline to enable central confirmation of BRAF or KRAS/NRAS mutations
  • Measurable, or non-measurable but evaluable disease as determined by RECIST
  • Adequate bone marrow function
  • Adequate hepatic and renal function
  • Adequate cardiovascular function
  • Negative serum β HCG test (female patients of childbearing potential only) within 72 hrs prior to first dose

Exclusion Criteria:

  • Patients with a history of primary central nervous system tumors or brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases
  • Current evidence of retinal disease; or ophthalmopathy as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO (e.g., optic disc cupping, visual field defects, IOP > 21 mm Hg)
  • Impaired cardio-/vascular function or clinically significant cardiovascular diseases, including any of the following:

    • History/evidence of acute coronary syndromes (including MI, unstable angina, CABG, coronary angioplasty, or stenting) ≤ 6 months prior to starting study drugs
    • Thromboembolic event (DVT, CVA, PE) ≤ 6 months prior to starting study
    • Symptomatic CHF, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality
    • Uncontrolled arterial hypertension, defined as BP > 140/100 mmHg (average of 3 consecutive readings)
  • History of melena, hematemesis or hemoptysis within the last 3 months
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL)

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01352273

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Moffitt 4
Tampa, Florida, United States, 33612
United States, Oregon
Oregon Health & Science University OHSU 3
Portland, Oregon, United States, 97239
United States, Utah
University of Utah / Huntsman Cancer Institute Huntman 2
Salt Lake City, Utah, United States, 84103
Canada, Alberta
Novartis Investigative Site
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H3T 1E3
Norway
Novartis Investigative Site
Oslo, Norway, NO-0379
Spain
Novartis Investigative Site
Madrid, Spain, 28050
Switzerland
Novartis Investigative Site
Zürich, Switzerland, 8091
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: NCT01352273     History of Changes
Other Study ID Numbers: CMEK162X2102, 2010-023812-14
Study First Received: May 2, 2011
Last Updated: March 25, 2014
Health Authority: United States: Food and Drug Administration
Spain: Health Authority
Norway: Health Authority
Germany: Health Authority
Switzerland: Health Authority
Canada: Health Authority

Keywords provided by Novartis:
advanced Solid tumors
harboring RAS
harboring BRAFV600E

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on April 17, 2014