Selumetinib in Cancers With BRAF Mutations

NCT ID: NCT00888134

Last Updated: 2016-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2015-01-31

Brief Summary

The purpose of this research study is to determine if selumetinib is safe and effective in treating patients with cancers with a mutated BRAF gene. Selumetinib is an investigational drug that works by blocking a protein called MEK, which is known to play a role in the growth of cancer cells lines and tumors that have a mutated BRAF gene. There are multiple types of cancers that have mutations in the BRAF gene and depend on the activity of this gene for their growth and survival.

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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').

OUTLINE:

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.

Conditions

Adult Solid Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (selumetinib)

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

Group Type: EXPERIMENTAL

Selumetinib

Intervention Type: DRUG

Given PO

Interventions

Selumetinib

Given PO

Intervention Type: DRUG

Other Intervention Names

ARRY-142886; AZD6244; MEK Inhibitor AZD6244

Eligibility Criteria

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 1.0
• 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 requirements
• 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%

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donald Lawrence

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Massachusetts General Hospital

Charlestown, Massachusetts, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

NCI-2013-00576

Identifier Type: REGISTRY

Identifier Source: secondary_id

P30CA006516

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062490

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR642346

Identifier Type: -

Identifier Source: secondary_id

N01CM62206

Identifier Type: NIH

Identifier Source: secondary_id

View Link

09-005

Identifier Type: OTHER

Identifier Source: secondary_id

8281

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2013-00576

Identifier Type: -

Identifier Source: org_study_id