Adult Solid NeoplasmPhase 2NCT00888134
Selumetinib in Cancers With BRAF Mutations
A Phase 2 study testing Selumetinib in people with Adult Solid Neoplasm, run by National Cancer Institute (NCI) at 5 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Solid Neoplasm
- What is being tested?
- Selumetinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 5 sitesUnited States
- Study dates
- Jul 2009to Jan 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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%
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Massachusetts General Hospital
Charlestown, Massachusetts, 02129
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase II Clinical Trial of the MEK 1/2 Inhibitor AZD6244 in Cancers With BRAF Mutations Identified by Prospective Genotypic Analysis
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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
- Being tested
- Selumetinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelumetinibDrug
Also called ARRY-142886, AZD6244, MEK Inhibitor AZD6244
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Selumetinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 4 years
Secondary outcomes (4)
AKT Pathway Activity
Correlation between response to AZD6244 and mutational analysis of AKT pathway (an intracellular signaling pathway important in regulating the cell cycle)
Measured: Up to 4 years
Objective Response Rate in Patients With Non-small Cell Lung Cancers and Colon Cancers
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.
Measured: Up to 4 years
Progression-free Survival
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.
Measured: 4 months
Sensitivity and Specificity of Detection of the BRAF V600E Mutation in CTC Using the CTC-chip
Measured: Up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2009 (estimated)
- Study startJul 2009
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adult Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Donald Lawrence, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00888134
- Sponsor's protocol ID
- NCI-2013-00576
- Other IDs
- NCI-2013-00576, P30CA006516, U01CA062490, CDR642346, N01CM62206, 09-005, 8281
- Status last verified
- Jul 2015
- First submitted
- 23 Apr 2009
- Last updated
- 15 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical Trial of the MEK 1/2 Inhibitor AZD6244 in Cancers With BRAF Mutations Identified by Prospective Genotypic Analysis
- ClinicalTrials.gov ID
- NCT00888134
- Acronym / sponsor ID
- NCI-2013-00576
- Conditions
- Adult Solid Neoplasm
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jul 2009
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 27 Apr 2009 (estimated)
- Results
- Posted 15 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (selumetinib) | Experimental | Drug: SelumetinibPatients receive selumetinib PO BID for 3 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SelumetinibAlso: ARRY-142886, AZD6244, MEK Inhibitor AZD6244Given PO | Drug | Treatment (selumetinib) |
Primary outcome
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).
4 secondary outcomes
AKT Pathway Activity
Time frame: Up to 4 years
Objective Response Rate in Patients With Non-small Cell Lung Cancers and Colon Cancers
Time frame: Up to 4 years
Progression-free Survival
Time frame: 4 months
Sensitivity and Specificity of Detection of the BRAF V600E Mutation in CTC Using the CTC-chip
Time frame: Up to 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donald Lawrence principal investigator
Massachusetts General Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Selumetinib in people with Adult Solid Neoplasm, run by National Cancer Institute (NCI) at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate in Patients With Cancers Other Than Melanoma (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2016.