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Selumetinib in Cancers With BRAF Mutations

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ClinicalTrials.gov Identifier: NCT00888134
Recruitment Status : Completed
First Posted : April 27, 2009
Results First Posted : January 15, 2016
Last Update Posted : January 15, 2016
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE April 23, 2009
First Posted Date  ICMJE April 27, 2009
Results First Submitted Date  ICMJE December 10, 2015
Results First Posted Date  ICMJE January 15, 2016
Last Update Posted Date January 15, 2016
Study Start Date  ICMJE July 2009
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 10, 2015)
Objective Response Rate in Patients With Cancers Other Than Melanoma [ Time Frame: 4 years ]
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).
Original Primary Outcome Measures  ICMJE
 (submitted: April 23, 2009)
To evaluate the objective response rate to AZD6244 in patients with cancers other than melanoma in which BRAF mutations have been identified prospectively. [ Time Frame: 3 years ]
Change History Complete list of historical versions of study NCT00888134 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2015)
  • AKT Pathway Activity [ Time Frame: Up to 4 years ]
    Correlation between response to AZD6244 and mutational analysis of AKT pathway (an intracellular signaling pathway important in regulating the cell cycle)
  • Objective Response Rate in Patients With Non-small Cell Lung Cancers and Colon Cancers [ Time Frame: Up to 4 years ]
    Percentage of participants with either colon cancer or non-small cell lung cancer 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.
  • Progression-free Survival [ Time Frame: 4 months ]
    Reported as percentage of participants alive and progression free at 4-months. Will be estimated using Kaplan-Meier survival curves. Confidence intervals will be calculated and reported.
  • Sensitivity and Specificity of Detection of the BRAF V600E Mutation in CTC Using the CTC-chip [ Time Frame: Up to 4 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2009)
  • To evaluate progression-free survival in subjects treated with AZD6244. [ Time Frame: 3 years ]
  • To obtain a preliminary estimate of the objective response rate in non-small cell lung cancers and colon cancers with BRAF mutations. [ Time Frame: 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Selumetinib in Cancers With BRAF Mutations
Official Title  ICMJE Phase II Clinical Trial of the MEK 1/2 Inhibitor AZD6244 in Cancers With BRAF Mutations Identified by Prospective Genotypic Analysis
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Adult Solid Neoplasm
Intervention  ICMJE Drug: Selumetinib
Given PO
Other Names:
  • ARRY-142886
  • AZD6244
  • MEK Inhibitor AZD6244
Study Arms  ICMJE Experimental: Treatment (selumetinib)
Patients receive selumetinib PO BID for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Drug: Selumetinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 24, 2015)
28
Original Estimated Enrollment  ICMJE
 (submitted: April 23, 2009)
66
Actual Study Completion Date  ICMJE January 2015
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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%
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00888134
Other Study ID Numbers  ICMJE NCI-2013-00576
NCI-2013-00576 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA006516 ( U.S. NIH Grant/Contract )
U01CA062490 ( U.S. NIH Grant/Contract )
CDR642346
N01CM62206 ( U.S. NIH Grant/Contract )
09-005 ( Other Identifier: Massachusetts General Hospital Cancer Center )
8281 ( Other Identifier: CTEP )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Donald Lawrence Massachusetts General Hospital
PRS Account National Cancer Institute (NCI)
Verification Date July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP