Selumetinib in Cancers With BRAF Mutations

NCT00888134 | Completed Phase 2 Results DMC

• 7 other identifiers: NCI-2013-00576P30CA006516U01CA062490CDR642346N01CM6220609-0058281
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 5

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.

Conditions

Adult Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate in Patients With Cancers Other Than Melanoma

  Percentage of participants achieving either complete response (disappearance of all target lesions) or partial response (at least a 30% decrease in the sum of the longest diameter of target lesions, when compared with baseline) using CT (computed tomography) scans (which are done every 6 weeks).

  4 years

Secondary Outcomes (4)

• AKT Pathway Activity

  Up to 4 years

• Objective Response Rate in Patients With Non-small Cell Lung Cancers and Colon Cancers

  Up to 4 years

• Progression-free Survival

  4 months

• Sensitivity and Specificity of Detection of the BRAF V600E Mutation in CTC Using the CTC-chip

  Up to 4 years

Study Arms (1)

Treatment (selumetinib)

EXPERIMENTAL

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

Drug: Selumetinib

Interventions

Selumetinib DRUG

Given PO

Also known as: ARRY-142886, AZD6244, MEK Inhibitor AZD6244

Treatment (selumetinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Interventions

AZD 6244

Results Point of Contact

• Title: Donald P. Lawrence
• Organization: Massachusetts General Hospital

dplawrence@mgh.harvard.edu

617-643-3614

Study Officials

• Donald Lawrence

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2009
• First Posted: April 27, 2009
• Study Start: July 1, 2009
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: January 15, 2016
• Results First Posted: January 15, 2016

Record last verified: 2015-07

Locations

US (5)