3rd Line GISTPhase 1NCT01468688
A Dose-finding Study of a Combination of Imatinib and BKM120 in the Treatment of 3rd Line GIST Patients
A Phase 1 study testing STI571 and BKM120 in people with 3rd Line GIST, run by Novartis Pharmaceuticals at 11 sites in 8 countries.
Trial summary
The purpose of this study is to determine a maximum tolerated dose and/or recommended phase 2 dose of a combination of imatinib and BKM120 in the treatment of 3rd line GIST patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- 3rd Line GIST
- What is being tested?
- STI571 and BKM120
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 11 sitesin 8 countries
- Study dates
- 20 Apr 2012to 29 Jul 2016
- 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
- Male or female patients ≥ 18 years of age
- WHO performance status (PS) of 0-2
- Histologically confirmed diagnosis of GIST that is unresectable or metastatic
- Available tissue specimen:
- Dose-escalation cohorts: patients must have available archival tumor tissue which can be shipped during the course of the study
- Dose-expansion cohort: patients must have available archival tumor tissue which can be shipped during the course of the study and must agree to a fresh pre-treatment biopsy.
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- Failed prior therapy with imatinib followed by sunitinib for the treatment of unresectable or metastatic GIST. Note the following specific criteria for the two phases of the trial:
- Dose-escalation cohorts: patients who failed prior therapy with imatinib and then have failed therapy with sunitinib. Treatment failure may be due to either disease progression on therapy (both imatinib and sunitinib) or intolerance to therapy (sunitinib). Dose-escalation cohort patients may have had additional lines of therapy not limited to imatinib and sunitinib.
- Dose-expansion cohort: patients must have documented disease progression on both imatinib and sunitinib. In addition, patients may have had no more than two lines of prior therapy (i.e. treatment with imatinib followed by treatment with sunitinib).
- Adjuvant imatinib will not count as a prior course of imatinib for the purposes of this criterion
Who cannot join
- Previous treatment with PI3-K inhibitors
- A medical history of any of the following mood disorders as judged by the Investigator or a psychiatrist:
- Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or thoughts, or homicidal thoughts (immediate risk of doing harm to others)
- ≥ CTCAE grade 3 anxiety
- When completing the patient questionnaires at screening:
- Meets the cut-off score of ≥ 10 in the nine item depression scale of the Patient Health Questionnaire (PHQ-9) or a cut-off of ≥ 15 in the Generalized Anxiety Disorder Assessment (GAD 7) mood scale respectively, or
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- Selects positive response of 1, 2, 3 to question number 9 regarding potential for suicidal thoughts or ideation in the PHQ-9 (independent of the total score of the PHQ-9)
- Severe and/or uncontrolled concurrent medical condition that, in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. acute or chronic liver, pancreatic, severe renal disease considered unrelated to study disease, chronic pulmonary disease including dyspnea at rest from any cause).
- Poorly controlled diabetes mellitus (defined as HbA1c > 8%)
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
11 sites in 8 countries.
11 sites in 8 countries
United States2 sites
Dana Farber Cancer Institute SC (2)
Boston, Massachusetts, 02215
Seattle Cancer Care Alliance Onc
Seattle, Washington, 98105
France2 sites
Novartis Investigative Site
Lyon, 69373
Novartis Investigative Site
Villejuif, 94805
United Kingdom2 sites
Novartis Investigative Site
London, SW3 6JJ
Novartis Investigative Site
Manchester, M20 9BX
About this study
Official title: A Multi-arm Dose-finding Phase Ib Multicenter Study of Imatinib in Combination With the Oral Phosphatidyl-inositol 3-kinase (PI3-K) Inhibitor BKM120 in Patients With Gastrointestinal Stromal Tumor (GIST) Who Failed Prior Therapy With Imatinib and Sunitinib
The purpose of this study is to determine a maximum tolerated dose and/or recommended phase 2 dose of a combination of imatinib and BKM120 in the treatment of 3rd line GIST patients.
- Conditions
- 3rd Line GIST
- Being tested
- STI571, BKM120
- Keywords
- Imatinib mesylate, BKM120, GIST
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
STI571Drug
BKM120Drug
BKM120 combination therapy
| Study group | Role | What they receive |
|---|---|---|
| STI571 (imatinib mesylate) and BKM120 | Experimental | The study will comprise of 2 parts. A dose escalation and a dose expansion part. Patients will receive increasing doses of BKM120 (40, 60, 80, 100 mg) in combination with 400mg imatinib daily until maximum tolerated dose (MTD) and rapid phase 2 dose (RP2D) is determined. 35 patients will enter the expansion phase with 18 patients having a pharmacokinetic (PK) run-in period of 8 days receiving imatinib monotherapy or BKM120 monotherapy. Receives: Drug: STI571 |
| STI571+BKM120 | Experimental | BKM120 Monotherapy 8 day run-in followed by STI571 and BKM120 combination therapy Receives: Drug: STI571; Drug: BKM120 |
| STI571 monotherapy run-in | Experimental | STI571 Monotherapy 8 day run-in followed by STI571 and BKM120 combination therapy Receives: Drug: STI571 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency and characteristics of dose limiting toxicities (DLTs) at each dose level during the first cycle of therapy
Dose limiting toxicity (DLT) will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) (v4.0.3), unless otherwise specified in the protocol.
Measured: 28 days (1st cycle)
Secondary outcomes (3)
Frequency and characteristics of DLTs at each dose level during the first cycle of therapy. Type, frequency and severity of adverse drug reactions.
Dose limiting toxicity (DLT) will be assessed using CTCAE (v4.0.3), unless otherwise specified in the protocol.
Measured: 28 days (1st cycle)
Imatinib and BKM120 plasma concentrations vs time profile, and basic PK parameters, including but not limited to AUC, Cmax, Tmax, CL/F.
Measured: 28 days (1st cycle)
Clinical benefit rate (CBR) defined as the rate of confirmed complete response (CR) or partial response (PR), or stable disease (SD) which lasts for at least 16 weeks.
Tumor response will be determined locally by the investigator sites according to Novartis guideline on the Response Evaluation Criteria in Solid Tumors, based on RECIST Version 1.1.
Measured: 28 days (1st cycle)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2011 (estimated)
- Study start20 Apr 2012
- Primary completion29 Jul 2016
- Study completion29 Jul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 3rd Line GISTStudies 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
- 60 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
- NCT01468688
- Sponsor's protocol ID
- CSTI571X2101
- Other IDs
- 2011-002938-39
- Status last verified
- Sep 2019
- First submitted
- 6 Nov 2011
- Last updated
- 21 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gelderblom H, Jones RL, George S, Valverde Morales C, Benson C, Jean-Yves Blay, Renouf DJ, Doi T, Le Cesne A, Leahy M, Hertle S, Aimone P, Brandt U, Schӧffski P. Imatinib in combination with phosphoinositol kinase inhibitor buparlisib in patients with gastrointestinal stromal tumour who failed prior therapy with imatinib and sunitinib: a Phase 1b, multicentre study. Br J Cancer. 2020 Apr;122(8):1158-1165. doi: 10.1038/s41416-020-0769-y. Epub 2020 Mar 9.
PubMed 32147671
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-arm Dose-finding Phase Ib Multicenter Study of Imatinib in Combination With the Oral Phosphatidyl-inositol 3-kinase (PI3-K) Inhibitor BKM120 in Patients With Gastrointestinal Stromal Tumor (GIST) Who Failed Prior Therapy With Imatinib and Sunitinib
- ClinicalTrials.gov ID
- NCT01468688
- Acronym / sponsor ID
- CSTI571X2101
- Conditions
- 3rd Line GIST
- Keywords
- Imatinib mesylate, BKM120, GIST
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 20 Apr 2012 (actual)
- Primary completion
- 29 Jul 2016 (actual)
- Study completion
- 29 Jul 2016 (actual)
- First posted
- 9 Nov 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.
The purpose of this study is to determine a maximum tolerated dose and/or recommended phase 2 dose of a combination of imatinib and BKM120 in the treatment of 3rd line GIST patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| STI571 (imatinib mesylate) and BKM120 | Experimental | Drug: STI571The study will comprise of 2 parts. A dose escalation and a dose expansion part. Patients will receive increasing doses of BKM120 (40, 60, 80, 100 mg) in combination with 400mg imatinib daily until maximum tolerated dose (MTD) and rapid phase 2 dose (RP2D) is determined. 35 patients will enter the expansion phase with 18 patients having a pharmacokinetic (PK) run-in period of 8 days receiving imatinib monotherapy or BKM120 monotherapy. |
| STI571+BKM120 | Experimental | Drug: STI571, Drug: BKM120BKM120 Monotherapy 8 day run-in followed by STI571 and BKM120 combination therapy |
| STI571 monotherapy run-in | Experimental | Drug: STI571STI571 Monotherapy 8 day run-in followed by STI571 and BKM120 combination therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female patients ≥ 18 years of age
- WHO performance status (PS) of 0-2
- Histologically confirmed diagnosis of GIST that is unresectable or metastatic
- Available tissue specimen:
- Failed prior therapy with imatinib followed by sunitinib for the treatment of unresectable or metastatic GIST. Note the following specific criteria for the two phases of the trial:
Key exclusion criteria (10 listed)
- Previous treatment with PI3-K inhibitors
- A medical history of any of the following mood disorders as judged by the Investigator or a psychiatrist:
- When completing the patient questionnaires at screening:
- Severe and/or uncontrolled concurrent medical condition that, in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. acute or chronic liver, pancreatic, severe renal disease considered unrelated to study disease, chronic pulmonary disease including dyspnea at rest from any cause).
- Poorly controlled diabetes mellitus (defined as HbA1c > 8%)
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 |
|---|---|---|
| STI571 | Drug | STI571 (imatinib mesylate) and BKM120, STI571 monotherapy run-in, STI571+BKM120 |
| BKM120BKM120 combination therapy | Drug | STI571+BKM120 |
Primary outcome
Frequency and characteristics of dose limiting toxicities (DLTs) at each dose level during the first cycle of therapy
Time frame: 28 days (1st cycle)
Dose limiting toxicity (DLT) will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) (v4.0.3), unless otherwise specified in the protocol.
3 secondary outcomes
Frequency and characteristics of DLTs at each dose level during the first cycle of therapy. Type, frequency and severity of adverse drug reactions.
Time frame: 28 days (1st cycle)
Imatinib and BKM120 plasma concentrations vs time profile, and basic PK parameters, including but not limited to AUC, Cmax, Tmax, CL/F.
Time frame: 28 days (1st cycle)
Clinical benefit rate (CBR) defined as the rate of confirmed complete response (CR) or partial response (PR), or stable disease (SD) which lasts for at least 16 weeks.
Time frame: 28 days (1st cycle)
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 21 Dec 2020.
- Derived from this study: PubMed 32147671Gelderblom H, Jones RL, George S, Valverde Morales C, Benson C, Jean-Yves Blay, Renouf DJ, Doi T, Le Cesne A, Leahy M, Hertle S, Aimone P, Brandt U, Schӧffski P. Imatinib in combination with phosphoinositol kinase inhibitor buparlisib in patients with gastrointestinal stromal tumour who failed prior therapy with imatinib and sunitinib: a Phase 1b, multicentre study. Br J Cancer. 2020 Apr;122(8):1158-1165. doi: 10.1038/s41416-020-0769-y. Epub 2020 Mar 9.
- Novartis' results databaseLink provided by the sponsor.
- Individual participant dataSharing planned: No
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
11 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing STI571 and BKM120 in people with 3rd Line GIST, run by Novartis Pharmaceuticals at 11 sites in 8 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 10 inclusion and 10 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 21 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 11 sites in United States, France, United Kingdom, Belgium, Canada and 3 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?
Frequency and characteristics of dose limiting toxicities (DLTs) at each dose level during the first cycle of therapy (time frame: 28 days (1st cycle)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01468688, which also lists 1 linked publication.
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 21 Dec 2020.