Advanced and Selected Solid TumorsPhase 1NCT01155453
A Study to Investigate Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BKM120 Plus GSK1120212 in Selected Advanced Solid Tumor Patients
A Phase 1 study testing BKM120 and GSK1120212 in people with Advanced and Selected Solid Tumors, run by Novartis Pharmaceuticals at 7 sites in 5 countries.
Trial summary
This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and /or recommended phase II dose (RP2D) and schedule for the PI3K (Phosphatidylinositol 3-Kinase) inhibitor BKM120 given in combination with the MEK inhibitor GSK1120212 in patients with selected, advanced solid… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced and Selected Solid Tumors
- What is being tested?
- BKM120 and GSK1120212
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 113 participants
- Where
- 7 sitesin 5 countries
- Study dates
- Apr 2010to Nov 2014
- 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 non resectable solid tumors
- Measurable or non-measurable, but evaluable disease as determined by RECIST 1.0
Who cannot join
- Patients with primary Central Nervous System (CNS) tumor or CNS tumor involvement.
- Clinically manifested diabetes mellitus - Unacceptable ocular/retinal conditions
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
United States2 sites
University of Texas/MD Anderson Cancer Center Dept of MD Anderson (8)
Houston, Texas, 77030-4009
University of California at Los Angeles Div. of Hematology/Oncology
Los Angeles, California, 90095
Spain2 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Seville, Andalusia, 41013
About this study
Official title: A Phase Ib, Open-label, Multi-center, Dose-escalation Study of Oral BKM120 in Combination With Oral GSK1120212 in Adult Patients With Selected Advanced Solid Tumors.
This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and /or recommended phase II dose (RP2D) and schedule for the PI3K (Phosphatidylinositol 3-Kinase) inhibitor BKM120 given in combination with the MEK inhibitor GSK1120212 in patients with selected, advanced solid tumors. The focus will be on tumors with RAS/RAF mutations and on triple negative breast cancer.
Both study drugs will be administered once daily orally on a continuous schedule, a treatment cycle is defined as 28 days.
Read more
Cohorts of at least 3 and up to a maximum of 6 patients eligible for the dose-determining set will be enrolled per dose combination below the MTD. The MTD is defined as the highest drug dosage not causing in the first cycle of treatment medically unacceptable, dose-limiting toxicity (DLT) in more than 33% of the treated patients.. At least 12 patients will be required at MTD and 6 patients at RP2D level to allow the evaluation of the combination's safety and pharmacokinetics or pharmacodynamics.
Upon declaration of MTD and/or RP2D, patients will be enrolled to an expansion part of the study, to further assess safety, as well as to learn more about the efficacy of the study drug combination.
- Expansion Arm 1 will consist of approximately 15 patients with RAS or BRAF mutant advanced NSCLC
- Expansion Arm 2 will consist of approximately 15 patients with RAS or BRAF-mutant ovarian cancer
- Expansion Arm 3 will consist of approximately 15 patients with RAS or BRAF-mutant pancreatic cancer
- Conditions
- Advanced and Selected Solid Tumors
- Being tested
- BKM120, GSK1120212
- Keywords
- BKM120, RAS RAF mutations,, triple negative breast cancer,, pancreatic cancer,, PI3K inhibitor,, MEK inhibitor
- Medical subject headings
- Triple Negative Breast Neoplasms, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BKM120Drug
GSK1120212Drug
| Study group | Role | What they receive |
|---|---|---|
| BKM120 + GSK1120212 DE | Experimental | Dose Escalation Receives: Drug: BKM120; Drug: GSK1120212 |
| BKM120 + GSK1120212 NSCLC patients | Experimental | Advanced RAS or BRAF mutant NSCLC patients Receives: Drug: BKM120; Drug: GSK1120212 |
| BKM120 + GSK1120212 ovarian cancer patients | Experimental | Advanced RAS or BRAF mutant ovarian cancer patients Receives: Drug: BKM120; Drug: GSK1120212 |
| BKM120 + GSK1120212 pancreatic cancer patients | Experimental | Advanced RAS or BRAF mutant pancreatic cancer patients Receives: Drug: BKM120; Drug: GSK1120212 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) and/or recommended phase II dose (RP2D) and schedule of BKM120+GSK1120212
Measured: in average 1 year
Secondary outcomes (5)
Measure the number of Adverse Event and laboratory values that fall outside of pre-determined ranges as a measure of Safety and tolerability of the oral combination of BKM120 and GSK1120212
Measured: in average 1 year
Determine the single and multiple dose pharmacokinetics of BKM120 and GSK1120212 in measurement of the plasma concentration profiles of BKM120 and GSK1120212
Measured: Assessed during the first Cycle (28 days) of treatment
Preliminary anti-tumor activity of the combination
Measured: Assessed every 8 weeks of treatment
Treatment-induced PI3K and MEK/ERK(Mitogen-activated protein kinase /extracellular-signal-regulated kinases) pathway signaling inhibition and evidence of biological activity in tumor and skin
Measured: Assessed every 2 weeks during the first cycle, then every 4 weeks
Molecular status (genetic alterations, protein expression and/or activation) of markers related to PI3K and ERK signaling in tumor tissue and blood and investigate their potential relationship to clinical responses
Measured: Assessed at baseline (pre-treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2010 (estimated)
- Study startApr 2010
- Primary completionNov 2014
- Study completionNov 2014
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.
- More trials run by Novartis PharmaceuticalsThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01155453
- Sponsor's protocol ID
- CBKM120B2101
- Other IDs
- 2009-017157-35, 2009
- Status last verified
- Jun 2016
- First submitted
- 17 Jun 2010
- Last updated
- 9 Dec 2020
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Open-label, Multi-center, Dose-escalation Study of Oral BKM120 in Combination With Oral GSK1120212 in Adult Patients With Selected Advanced Solid Tumors.
- ClinicalTrials.gov ID
- NCT01155453
- Acronym / sponsor ID
- CBKM120B2101
- Conditions
- Advanced and Selected Solid Tumors
- Keywords
- BKM120, RAS RAF mutations,, triple negative breast cancer,, pancreatic cancer,, PI3K inhibitor,, MEK inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Apr 2010
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 1 Jul 2010 (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 an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and /or recommended phase II dose (RP2D) and schedule for the PI3K (Phosphatidylinositol 3-Kinase) inhibitor BKM120 given in combination with the MEK inhibitor GSK1120212 in patients with selected, advanced solid tumors. The focus will be on tumors with RAS/RAF mutations and on triple negative breast cancer.
Both study drugs will be administered once daily orally on a continuous schedule, a treatment cycle is defined as 28 days.
Cohorts of at least 3 and up to a maximum of 6 patients eligible for the dose-determining set will be enrolled per dose combination below the MTD. The MTD is defined as the highest drug dosage not causing in the first cycle of treatment medically unacceptable, dose-limiting toxicity (DLT) in more than 33% of the treated patients.. At least 12 patients will be required at MTD and 6 patients at RP2D level to allow the evaluation of the combination's safety and pharmacokinetics or pharmacodynamics.
Upon declaration of MTD and/or RP2D, patients will be enrolled to an expansion part of the study, to further assess safety, as well as to learn more about the efficacy of the study drug combination.
- Expansion Arm 1 will consist of approximately 15 patients with RAS or BRAF mutant advanced NSCLC
- Expansion Arm 2 will consist of approximately 15 patients with RAS or BRAF-mutant ovarian cancer
- Expansion Arm 3 will consist of approximately 15 patients with RAS or BRAF-mutant pancreatic cancer
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| BKM120 + GSK1120212 DE | Experimental | Drug: BKM120, Drug: GSK1120212Dose Escalation |
| BKM120 + GSK1120212 NSCLC patients | Experimental | Drug: BKM120, Drug: GSK1120212Advanced RAS or BRAF mutant NSCLC patients |
| BKM120 + GSK1120212 ovarian cancer patients | Experimental | Drug: BKM120, Drug: GSK1120212Advanced RAS or BRAF mutant ovarian cancer patients |
| BKM120 + GSK1120212 pancreatic cancer patients | Experimental | Drug: BKM120, Drug: GSK1120212Advanced RAS or BRAF mutant pancreatic cancer patients |
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 non resectable solid tumors
- Measurable or non-measurable, but evaluable disease as determined by RECIST 1.0
Key exclusion criteria (3 listed)
- Patients with primary Central Nervous System (CNS) tumor or CNS tumor involvement.
- Clinically manifested diabetes mellitus - Unacceptable ocular/retinal conditions
- Other protocol-defined inclusion/exclusion criteria may apply.
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 |
|---|---|---|
| BKM120 | Drug | BKM120 + GSK1120212 DE, BKM120 + GSK1120212 NSCLC patients, BKM120 + GSK1120212 ovarian cancer patients, BKM120 + GSK1120212 pancreatic cancer patients |
| GSK1120212 | Drug | BKM120 + GSK1120212 DE, BKM120 + GSK1120212 NSCLC patients, BKM120 + GSK1120212 ovarian cancer patients, BKM120 + GSK1120212 pancreatic cancer patients |
Primary outcome
Maximum Tolerated Dose (MTD) and/or recommended phase II dose (RP2D) and schedule of BKM120+GSK1120212
Time frame: in average 1 year
5 secondary outcomes
Measure the number of Adverse Event and laboratory values that fall outside of pre-determined ranges as a measure of Safety and tolerability of the oral combination of BKM120 and GSK1120212
Time frame: in average 1 year
Determine the single and multiple dose pharmacokinetics of BKM120 and GSK1120212 in measurement of the plasma concentration profiles of BKM120 and GSK1120212
Time frame: Assessed during the first Cycle (28 days) of treatment
Preliminary anti-tumor activity of the combination
Time frame: Assessed every 8 weeks of treatment
Treatment-induced PI3K and MEK/ERK(Mitogen-activated protein kinase /extracellular-signal-regulated kinases) pathway signaling inhibition and evidence of biological activity in tumor and skin
Time frame: Assessed every 2 weeks during the first cycle, then every 4 weeks
Molecular status (genetic alterations, protein expression and/or activation) of markers related to PI3K and ERK signaling in tumor tissue and blood and investigate their potential relationship to clinical responses
Time frame: Assessed at baseline (pre-treatment)
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 9 Dec 2020.
- Results for CBKM120B2101 on the Novartis Clinical Trial websiteLink provided by the sponsor.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BKM120 and GSK1120212 in people with Advanced and Selected Solid Tumors, run by Novartis Pharmaceuticals at 7 sites in 5 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 3 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 9 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Spain, Belgium, Canada, Switzerland. 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?
Maximum Tolerated Dose (MTD) and/or recommended phase II dose (RP2D) and schedule of BKM120+GSK1120212 (time frame: in average 1 year). 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 9 Dec 2020.