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

NCT ID: NCT01352273

Last Updated: 2020-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2013-09-30

Brief 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.

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MEK162 + RAF265

Group Type: EXPERIMENTAL

MEK162 + RAF265

Intervention Type: DRUG

Interventions

MEK162 + RAF265

Intervention Type: DRUG

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Array Biopharma, now a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

H. Lee Moffitt Cancer Center & Research Institute Moffitt 4

Tampa, Florida, 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

Pfizer Investigative Site

Edmonton, Alberta, Canada

Pfizer Investigative Site

Montreal, Quebec, Canada

Pfizer Investigative Site

Oslo, , Norway

Pfizer Investigative Site

Madrid, , Spain

Pfizer Investigative Site

Zurich, , Switzerland

Countries

United States; Canada; Norway; Spain; Switzerland

Other Identifiers

2010-023812-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CMEK162X2102

Identifier Type: -

Identifier Source: org_study_id