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Phase II Clinical Trial of the MEK 1/2 Inhibitor AZD6244 in Cancers With BRAF Mutations Identified by Prospective Genotypic Analysis

Phase 2
18 Years
Open (Enrolling)
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase II Clinical Trial of the MEK 1/2 Inhibitor AZD6244 in Cancers With BRAF Mutations Identified by Prospective Genotypic Analysis


I. To evaluate the objective response rate to AZD6244 in patients with cancers other than
melanoma in which BRAF mutations have been identified prospectively.


I. To evaluate progression-free survival in subjects treated with AZD6244. II. To obtain a
preliminary estimate of the objective response rate in non-small cell lung cancers and colon
cancers with BRAF mutations.

III. To explore biologic correlates of responsiveness to AZD6244, and specifically to
correlate AKT pathway activity with sensitivity to MEK inhibition in the BRAF mutant class
of tumors.

IV. To estimate the sensitivity and specificity of detection of the BRAF V600E mutation in
circulating tumor cells (CTC) using a microfluidic platform (the 'CTC-chip').


Patients receive selumetinib orally (PO) twice daily (BID) for 3 weeks. Courses repeat every
3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year,
every 6 months for 1 year, and then annually thereafter.

Inclusion Criteria:

- Ability to understand and willingness to sign a written informed consent document

- Histologically confirmed metastatic or unresectable solid tumor

- Results from tumor tissue analysis that show a glutamic acid-for-valine substitution
at amino acid position 600 in the BRAF gene (V600E) or other activating BRAF
mutation, as determined by high-throughput genotyping

- Patients may have received any number of prior systemic treatments for their cancer

- At least one measurable site of disease by CT, according to standard RECIST criteria

- ECOG performance status 0-1

- Absolute neutrophil count > 1500 per cubic mm

- Platelet count > 100,000 per cubic mm

- Hemoglobin > 9 g/dl

- Serum bilirubin < 1.5 x upper limit of normal

- Serum AST and ALT < 2.5 x upper limit of normal (=< 5 x upper limit of normal, for
liver metastases)

- Serum creatinine < 1.5 x upper limit of normal

- For women of childbearing potential, negative serum pregnancy test and use of
physician-approved method of birth control throughout the study

Exclusion Criteria:

- Estimated life expectancy > 12 weeks

- Patients with melanoma

- Have received chemotherapy or radiotherapy within 4 weeks prior to entering the study
(6 weeks for nitrosoureas or mitomycin C), or a targeted therapy within 2 weeks prior
to entering the study

- Have not recovered from adverse events due to agents previously administered (CTCAE
v3 grade 1 or baseline)

- Currently receiving other investigational agents

- Known brain metastases, unless treated and stable off of corticosteroids for at least
four weeks

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to AZD6244

- Prior treatment with a selective inhibitor of RAF or MEK (e.g., RAF265); (note: prior
sorafenib is allowed)

- Uncontrolled intercurrent illness, including but not limited to:

- Clinically significant active infection

- Symptomatic congestive heart failure, unstable angina pectoris, and/or cardiac
arrhythmia other than atrial fibrillation

- Psychiatric illness/social situations that would limit compliance with study

- Refractory nausea or vomiting, swallowing disorder, or malabsorption syndrome that
would interfere with swallowing or absorbing the study medication

- Pregnant and/or breast-feeding women

- Previous or concurrent malignancy, except for the following circumstances:

- Disease-free for at least three years and deemed by investigator to be at low
risk for recurrence of that malignancy

- Individuals with the following cancers are eligible if diagnosed and treated
within the past 5 years: cervical cancer in situ, and basal cell or squamous
cell carcinoma of the skin)

- History of solid organ transplantation or other condition requiring the use of
immunosuppressive medications

- Uncontrolled hypertension (systolic BP >= 150 or diastolic BP >= 100 that cannot be
controlled with medications)

- A mean left ventricular ejection fraction (LVEF) less than 45%

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response rate in patients with cancers other than melanoma

Outcome Time Frame:

Up to 4 years

Safety Issue:


Principal Investigator

Donald Lawrence

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

July 2009

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific



Massachusetts General Hospital Cancer Center Boston, Massachusetts  02114