Clinical trial NCT00959127: A Study of ARRY-438162 (MEK162) in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Advanced or Metastatic Biliary Cancer
Metastatic Colorectal Cancer
Keywords: Colorectal Adenocarcinoma
Colon Cancer
Rectal Cancer
Lead sponsor: Array BioPharma
Sponsor class: INDUSTRY
First posted: 2009-08-14
Enrollment: 93
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 Phase 1 study during which patients with advanced solid tumors will receive investigational study drug ARRY-438162 (MEK162).

This study has 3 parts. In the first part, patients with advanced solid tumors will receive increasing doses of study drug in order to achieve the highest dose of the study drug possible that will not cause unacceptable side effects. Approximately 30 patients from the US will be enrolled in Part 1. (Active, not recruiting)

In the second part of the study, patients with advanced or metastatic biliary cancer will receive the best dose of study drug determined from the first part of the study and will be followed to see what side effects and effectiveness the study drug has, if any, in treating the cancer. Approximately 25 patients from the US will be enrolled in Part 2. (Active, not recruiting)

In the third part of the study, patients with metastatic colorectal cancer (CRC) will receive the best dose of the study drug determined from the first part of the study and will be followed to see what side effects and effectiveness the study drug has, if any, in treating the cancer. Approximately 25 patients with KRAS mutation (Active, not recruiting) and 15 patients with BRAF mutation (Active, not recruiting) from the US will be enrolled in Part 3.


Eligibility criteria: Key Inclusion Criteria (for Part 3):

* A histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma which is metastatic (measurable disease).
* Documented KRAS- or BRAF- tumor mutation.
* Previously treated with or unsuitable for treatment with 5-Fluorouracil (5-FU), oxaliplatin, irinotecan and, if available, bevacizumab.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
* Additional criteria exist.

Key Exclusion Criteria (for Part 3):

* Uncontrolled or symptomatic brain metastases (if the patient has brain metastases and is on steroids, the steroid dose must have been stable for at least 30 days).
* History of central serous retinopathy, retinopathy visible at baseline that would be considered a risk factor for central serous retinopathy or retinal vein occlusion.
* Concomitant malignancies or previous malignancies with less than a 2-year disease free interval at the time of enrollment; patients with adequately resected basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or stage A low grade prostate cancer may enroll irrespective of the time of diagnosis.
* Prior treatment with a MEK inhibitor.
* Treatment with prior chemotherapy, anticancer immunotherapy, monoclonal antibodies or other protein or peptide therapeutics within 21 days of the first dose of study drug.
* Treatment with a small molecule targeted agent or anticancer hormonal therapy within 14 days of the first dose of study drug.
* Treatment with prior radiotherapy within 28 days of initiating study drug (if the radiation portal covered ≤ 10% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy).
* Major surgery within 4 weeks or minor surgery within 7 days prior to the first dose of study drug.
* Known positive serology for the human immunodeficiency virus (HIV), hepatitis C, and/or active hepatitis B.
* Additional criteria exist.

Primary outcomes:
measure: Establish the maximum tolerated dose (MTD) of the study drug.
timeFrame: Part 1, one year
measure: Characterize the safety profile of the study drug in terms of adverse events, clinical laboratory tests and electrocardiograms.
timeFrame: Parts 1, 2 and 3: two years
measure: Characterize the pharmacokinetics (PK) of the study drug and metabolite.
timeFrame: Parts 1, 2 and 3: two years
Secondary outcomes:
measure: Assess the efficacy of the study drug in terms of tumor response, duration of response, duration of stable disease, progression-free survival and overall survival.
timeFrame: Parts 1, 2 and 3: two years
measure: Assess possible PK/pharmacodynamic (PD) or PK/efficacy and safety correlations.
timeFrame: Parts 1, 2 and 3: two years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: