Randomized Phase II Study of AZD6244 (Mitogen-activated Protein Kinase Inhibitor) MEK-Inhibitor With Erlotinib in KRAS Wild Type Advanced Non-Small Cell Lung Cancer (NSCLC) and a Randomized Phase II Study of AZD6244 With Erlotinib in Mutant KRAS Adva...

Completed · Phase 2

Conditions studied: Non Small Cell Lung Carcinoma

In brief

Background: AZD6244 (ARRY-142886) is an investigational anticancer drug that is designed to block a critical component (MEK (methyl ethyl ketone)) of a pathway (MAP (mitogen-activated protein) kinase pathway) that causes some lung cancer cells to grow. The MAP kinase pathway could be overactive in a proportion of lung cancers, including some which also have another mutation in a protein known as KRAS (Kirsten rat sarcoma viral oncogene homolog). Approximately 20% of lung cancers have KRAS mutations which can make some cancer treatments including erlotinib, a standard anticancer treatment drug less effective. Researchers are interested in determining whether AZD6244 is effective in treating advanced NSCLC (non small cell lung cancer), including KRAS mutated lung cancer that has not responded to standard therapy. Objectives: To determine the effectiveness of AZD6244, either alone or in combination with erlotinib, in preventing tumor growth in individuals with NSCLC. Eligibility: Individuals at least 18 years of age who have been diagnosed with advanced NSCLC that has not responded to standard therapy. Design: * Participants will be screened with a medical history, physical examination, blood tests, imaging studies, and potentially, tumor biopsy tests to determine whether a participant's NSCLC contains mutations in the KRAS protein. * Participants will be divided into two groups based on the status of the KRAS protein in their NSCLC tumor cells: * Individuals with normal KRAS protein: Half will receive AZD6244 and erlotinib, and half will receive only erlotinib. * Individuals with mutated KRAS protein: Half will receive AZD6244 and erlotinib, and half will receive only AZD6244. * Participants will take their assigned medications daily (on an empty stomach in the morning and/or evening, depending on the treatment) for 28-day cycles of treatment. Participants will also keep a medication diary to record any side effects. * Participants will have frequent blood tests during the first cycle of treatment, and will have imaging studies or other tests as required by the study researchers. Participants may also have an additional tumor biopsy after the end of the first treatment cycle. * Treatment will continue until the disease progresses, significant side effects develop, the participant chooses to leave the study, or the researchers end the study....

Key facts

Study ID: NCT01229150
Run by: National Cancer Institute (NCI)
People needed: 89
Starts: 2010-10-26
Expected to finish: 2015-11-21
Last updated by the study team: 2017-05-23

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered to less than or equal to grade 1 toxicities from adverse events due to agents administered more than 4 weeks earlier.
Patients may not be receiving any other investigational agents.
In general, patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients who have completed primary treatment of their brain metastasis by surgery or radiotherapy and have been off steroids (with the exception of maintenance replacement steroids) and anti-seizure medications for greater than one month without progression of neurological symptoms are eligible for enrollment in this trial. Stability of treated brain metastases should be confirmed by repeat imaging studies (CT brain or MRI (magnetic resonance imaging) brain) performed at least one month after completion of treatment.
Previous MEK (methyl ethyl ketone) inhibitor or prior treatment with EGFR TKI (tyrosine kinase inhibitor).
Major surgery or significant traumatic injury occurring within 21 days prior to treatment.
Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogrens syndrome), congenital abnormality (e.g., Fuchs dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test).
Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV (intravenous) alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease.
Patients with uncontrolled hypertension already on optimal medication, patients with class II or greater heart failure, any current or prior history of cardiomyopathy. Patient with baseline LVEF (left ventricular ejection fraction) less than 50%, atrial fibrillation, recent myocardial infarction, or unstable ischemic heart disease.
Patients with QTc (corrected QT interval) interval greater than 450 msecs or other factors that increase the risk of QT (Q wave, T wave) prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that meets New York Heart Association (NYHA) class III and IV definitions are excluded. This does not include QTc prolongation secondary to a paced rhythm. If a patient has a paced rhythm, QTc levels less than or equal to 500 (Grade 1) are allowed and patients with QTc > 500 are excluded.
Required use of a concomitant medication that can prolong the QT interval. A comprehensive list of agents with the potential to cause QTc prolongation can be found at http://www.arizonacert.org/medical-pros/drug-lists/drug-lists.htm.
Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, Hepatitis B or C, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study because AZD6244 is a MEK- Inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD6244, breastfeeding should be discontinued if the mother is treated with AZD6244. These potential risks may also apply to other agents used in this study.
HIV (human immunodeficiency virus) -positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD6244. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
INCLUSION OF WOMEN AND MINORITIES:
Both men and women and members of all races and ethnic groups are eligible for this trial.

Where it is running

University of California, Davis — Davis, California, United States
University of Southern California Health Sciences Campus — Los Angeles, California, United States
City of Hope Medical Group — South Pasadena, California, United States
University of Chicago Medical Center — Chicago, Illinois, United States
National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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