Advanced and Selected Solid TumorsPhase 1NCT01449058
A Phase Ib Study of MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors
A Phase 1 study testing BYL719 and MEK162 in people with Advanced and Selected Solid Tumors and AML, run by Array BioPharma at 16 sites in 7 countries.
Trial summary
This is a multi-center, open-label, dose-finding, phase Ib study to estimate the maximum tolerated dose(s) (MTD(s)) and/or recommended dose(s) for expansion (RDE(s)) for the orally administered combination of BYL719 and MEK162. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced and Selected Solid Tumors, AML, High Risk and Very High Risk MDS
- What is being tested?
- BYL719 and MEK162
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 139 participants
- Where
- 16 sitesin 7 countries
- Study dates
- Mar 2012to 15 Aug 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Histologically/cytologically confirmed, advanced solid tumors, AML or high risk and very high risk MDS
- Measurable disease as determined by RECIST 1.1
Who cannot join
- Primary CNS tumor or CNS tumor involvement
- Diabetes mellitus
- Unacceptable ocular/retinal conditions
- Clinically significant cardiac disease or impaired cardiac function
Trial locations and contacts
16 sites in 7 countries.
16 sites in 7 countries
United States8 sites
Massachusetts General Hospital CCPO
Boston, Massachusetts, 02114
Northwestern Memorial Hospital
Chicago, Illinois, 60611
University of Texas/MD Anderson Cancer Center Dept. of Onc.
Houston, Texas, 77030-4009
University of California San Diego - Moores Cancer Center Dept Onc
La Jolla, California, 92093-0658
Memorial Sloan Kettering Cancer Center Onc. Dept
New York, New York, 90033
University of Utah / Huntsman Cancer Institute Huntsman (3)
Salt Lake City, Utah, 84103
H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC
Tampa, Florida, 33612
Montefiore Medical Center SC
The Bronx, New York, 10461
Italy2 sites
Array BioPharma Investigative Site
Milan, MI, 20133
Array BioPharma Investigative Site
Roma, RM, 00168
Spain2 sites
Array BioPharma Investigative Site
Barcelona, Catalonia, 08035
Array BioPharma Investigative Site
Barcelona, Catalonia, 08036
Australia1 site
Array BioPharma Investigative Site
Parkville, Victoria, 3050
United Kingdom1 site
Array BioPharma Investigative Site
Sutton, SM2 5PT
About this study
Official title: A Phase Ib Open-label, Multi-center, Dose Escalation and Expansion Study of Orally Administered MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors
This is a multi-center, open-label, dose-finding, phase Ib study to estimate the maximum tolerated dose(s) (MTD(s)) and/or recommended dose(s) for expansion (RDE(s)) for the orally administered combination of BYL719 and MEK162. This combination will be explored in adult patients with advanced CRC, esophageal cancer, pancreatic cancer, NSCLC, ovarian cancer, or other advanced solid tumors and in adult patients with AML or high risk and very high risk MDS, with documented RAS or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RDE, four expansion arms will be opened in order to further assess the safety and preliminary activity of the combination of BYL719 and MEK162 in specific patient populations.
- Being tested
- BYL719, MEK162
- Keywords
- Advanced solid tumor,, AML, high risk and very high risk MDS, dose escalation,, RAS/BRAF mutation,, PI3K inhibitor,, MEK inhibitor,, BYL719,, MEK162
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BYL719Drug
taken orally
MEK162Drug
taken orally
| Study group | Role | What they receive |
|---|---|---|
| BYL719 + MEK162 | Experimental | BYL719 plus MEK162. Dose escalation with a starting dose for the first cohort of 200mg QD BYL719 and 30mg BID MEK162 Receives: Drug: BYL719; Drug: MEK162 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose Limiting Toxicities (DLT)
Toxicity will be assessed using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0 unless otherwise specified. A DLT is defined as an adverse event or abnormal laboratory value assessed as at least possibly related to the study medication, occurs ≤ 28 days following the first dose of BYL719 and MEK162 (Cycle 1), and meets any of the protocol-specified DLT criteria.
Measured: during the first cycle (28 days) of treatment with BYL719 and MEK162
Secondary outcomes (7)
Number of participants with adverse events and serious adverse events
All AEs and SAEs will be collected in accordance with the protocol and assessed for relatedness to study drug combination.
Measured: Assessed from Cycle 1 Day 1 until treatment discontinuation
Overall response rate
Overall response rate (ORR) is the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR).
Measured: Assessed every 8 weeks until disease progression
Time to progression
Time to progression (TTP) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient has not had an event, time to progression is censored at the date of last adequate tumor assessment.
Measured: Assessed every 8 weeks until disease progression
Progression free survival
Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
Measured: Assessed every 8 weeks until disease progression
Time versus plasma concentration profiles of BYL719 and MEK162
Blood concentrations of MEK162 and its metabolite (AR00426032) and BYL719 will be assessed during the first cycle of treatment.
Measured: Assessed during the first cycle of treatment
Correlation of baseline mutation or amplification status (PIK3CA, KRAS, NRAS and BRAF) and clinical anti-tumor activity outcome
Collect baseline genetic mutation/alteration status to investigate the potential relationship to anti-tumor activity.
Measured: Assessed at Baseline (pre-treatment)
Clinical benefit rate
The clinical benefit rate is defined as the proportion of patients with complete remission, complete remission with incomplete blood count recovery, partial remission, minor response or stable disease for > 15 weeks
Measured: Assessed every 4 weeks for 3 months and every 3 months for 6 months followed by every 6 months thereafter until disease progression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2011 (estimated)
- Study startMar 2012
- Primary completion31 Aug 2016
- Study completion15 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced and Selected Solid TumorsStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 139 participants (actual)
Sponsor and investigators
- Lead sponsor
- Array BioPharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Array BioPharma, Study director, 303-381-6604
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01449058
- Sponsor's protocol ID
- CMEK162X2109
- Other IDs
- 2011-002578-21
- Status last verified
- Sep 2017
- First submitted
- 6 Oct 2011
- Last updated
- 2 Oct 2017
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Open-label, Multi-center, Dose Escalation and Expansion Study of Orally Administered MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01449058
- Acronym / sponsor ID
- CMEK162X2109
- Keywords
- Advanced solid tumor,, AML, high risk and very high risk MDS, dose escalation,, RAS/BRAF mutation,, PI3K inhibitor,, MEK inhibitor,, BYL719,
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 139 participants (actual)
- Lead sponsor
- Array BioPharmaIndustry (pharma, biotech, devices)
- Study start
- Mar 2012
- Primary completion
- 31 Aug 2016 (actual)
- Study completion
- 15 Aug 2017 (actual)
- First posted
- 7 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-center, open-label, dose-finding, phase Ib study to estimate the maximum tolerated dose(s) (MTD(s)) and/or recommended dose(s) for expansion (RDE(s)) for the orally administered combination of BYL719 and MEK162. This combination will be explored in adult patients with advanced CRC, esophageal cancer, pancreatic cancer, NSCLC, ovarian cancer, or other advanced solid tumors and in adult patients with AML or high risk and very high risk MDS, with documented RAS or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RDE, four expansion arms will be opened in order to further assess the safety and preliminary activity of the combination of BYL719 and MEK162 in specific patient populations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BYL719 + MEK162 | Experimental | Drug: BYL719, Drug: MEK162BYL719 plus MEK162. Dose escalation with a starting dose for the first cohort of 200mg QD BYL719 and 30mg BID MEK162 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Histologically/cytologically confirmed, advanced solid tumors, AML or high risk and very high risk MDS
- Measurable disease as determined by RECIST 1.1
Key exclusion criteria (4 listed)
- Primary CNS tumor or CNS tumor involvement
- Diabetes mellitus
- Unacceptable ocular/retinal conditions
- Clinically significant cardiac disease or impaired cardiac function
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 |
|---|---|---|
| BYL719taken orally | Drug | BYL719 + MEK162 |
| MEK162taken orally | Drug | BYL719 + MEK162 |
Primary outcome
Incidence of Dose Limiting Toxicities (DLT)
Time frame: during the first cycle (28 days) of treatment with BYL719 and MEK162
Toxicity will be assessed using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0 unless otherwise specified. A DLT is defined as an adverse event or abnormal laboratory value assessed as at least possibly related to the study medication, occurs ≤ 28 days following the first dose of BYL719 and MEK162 (Cycle 1), and meets any of the protocol-specified DLT criteria.
7 secondary outcomes
Number of participants with adverse events and serious adverse events
Time frame: Assessed from Cycle 1 Day 1 until treatment discontinuation
Overall response rate
Time frame: Assessed every 8 weeks until disease progression
Time to progression
Time frame: Assessed every 8 weeks until disease progression
Progression free survival
Time frame: Assessed every 8 weeks until disease progression
Time versus plasma concentration profiles of BYL719 and MEK162
Time frame: Assessed during the first cycle of treatment
Correlation of baseline mutation or amplification status (PIK3CA, KRAS, NRAS and BRAF) and clinical anti-tumor activity outcome
Time frame: Assessed at Baseline (pre-treatment)
Clinical benefit rate
Time frame: Assessed every 4 weeks for 3 months and every 3 months for 6 months followed by every 6 months thereafter until disease progression
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2017.
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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.
Array BioPharma study director
303-381-6604
16 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BYL719 and MEK162 in people with Advanced and Selected Solid Tumors and AML, run by Array BioPharma at 16 sites in 7 countries.
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 2 inclusion and 4 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 2 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Italy, Spain, Australia, France and 2 more countries. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of Dose Limiting Toxicities (DLT) (time frame: during the first cycle (28 days) of treatment with BYL719 and MEK162). 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 2 Oct 2017.