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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01352273
• Other study ID #: CMEK162X2102
• Secondary ID: 2010-023812-14
• Status: Completed
• Phase: Phase 1
• Start date: June 2011
• Est. completion date: September 2013

Study information

• Verified date: September 2020
• Source: Array BioPharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß 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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• MEK162 + RAF265

Locations

Country	Name	City	State
Canada	Pfizer Investigative Site	Edmonton	Alberta
Canada	Pfizer Investigative Site	Montreal	Quebec
Norway	Pfizer Investigative Site	Oslo
Spain	Pfizer Investigative Site	Madrid
Switzerland	Pfizer Investigative Site	Zürich
United States	Oregon Health & Science University OHSU 3	Portland	Oregon
United States	University of Utah / Huntsman Cancer Institute Huntman 2	Salt Lake City	Utah
United States	H. Lee Moffitt Cancer Center & Research Institute Moffitt 4	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Array Biopharma, now a wholly owned subsidiary of Pfizer

Countries where clinical trial is conducted

United States,  Canada,  Norway,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose Limiting Toxicities		during the first 28 days of treatment with RAF265 and MEK162
Secondary	Number of participants with adverse events and serious adverse events		18 months
Secondary	assess preliminary anti-tumor activity of the combination	CT scan will be performed	every 8 weeks of treatment
Secondary	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		18 months
Secondary	Time versus plasma concentration profiles of RAF265 and MEK162		10 months