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

NCT01352273 | Completed Phase 1

• 2 other identifiers: CMEK162X21022010-023812-14
• Study Type: interventional
• Target: 69
• Locations: 5 countries
• Sites: 8

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

Keywords

advanced Solid tumors; harboring RAS; harboring BRAFV600E

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose Limiting Toxicities

  during the first 28 days of treatment with RAF265 and MEK162

Secondary Outcomes (4)

• Number of participants with adverse events and serious adverse events

  18 months

• assess preliminary anti-tumor activity of the combination

  every 8 weeks of treatment

• 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

• Time versus plasma concentration profiles of RAF265 and MEK162

  10 months

Study Arms (1)

MEK162 + RAF265

EXPERIMENTAL

Drug: MEK162 + RAF265

Interventions

MEK162 + RAF265 DRUG

MEK162 + RAF265

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Array Biopharma, now a wholly owned subsidiary of Pfizer: lead

Study Sites (8)

H. Lee Moffitt Cancer Center & Research Institute Moffitt 4

Tampa, Florida, 33612, United States

Location

Oregon Health & Science University OHSU 3

Portland, Oregon, 97239, United States

Location

University of Utah / Huntsman Cancer Institute Huntman 2

Salt Lake City, Utah, 84103, United States

Location

Pfizer Investigative Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

Pfizer Investigative Site

Montreal, Quebec, H3T 1E3, Canada

Location

Pfizer Investigative Site

Oslo, NO-0379, Norway

Location

Pfizer Investigative Site

Madrid, 28050, Spain

Location

Pfizer Investigative Site

Zurich, 8091, Switzerland

Location

MeSH Terms

Interventions

binimetinib; RAF265

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2011
• First Posted: May 11, 2011
• Study Start: June 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: September 30, 2020

Record last verified: 2020-09

Locations

US (3); NO (1); ES (1); CH (1); CA (2)