Clinical trial NCT01352273: MEK162 and RAF265 in Adult Patients With Advanced Solid Tumors Harboring RAS or BRAFV600E Mutations
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: advanced Solid tumors
harboring RAS
harboring BRAFV600E
Lead sponsor: Array BioPharma
Sponsor class: INDUSTRY
First posted: 2011-05-11
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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)

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities
timeFrame: during the first 28 days of treatment with RAF265 and MEK162
Secondary outcomes:
measure: Number of participants with adverse events and serious adverse events
timeFrame: 18 months
measure: assess preliminary anti-tumor activity of the combination
timeFrame: every 8 weeks of treatment
measure: 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
timeFrame: 18 months
measure: Time versus plasma concentration profiles of RAF265 and MEK162
timeFrame: 10 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute Moffitt 4
state: Florida
city: Portland
country: United States
facility: Oregon Health & Science University OHSU 3
state: Oregon
city: Salt Lake City
country: United States
facility: University of Utah / Huntsman Cancer Institute Huntman 2
state: Utah
city: Edmonton
country: Canada
facility: Pfizer Investigative Site
state: Alberta
city: Montreal
country: Canada
facility: Pfizer Investigative Site
state: Quebec
city: Oslo
country: Norway
facility: Pfizer Investigative Site
city: Madrid
country: Spain
facility: Pfizer Investigative Site
city: Zürich
country: Switzerland
facility: Pfizer Investigative Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: