A Dose-finding Study of a Combination of Imatinib and BKM120 in the Treatment of 3rd Line GIST Patients
NCT ID: NCT01468688
Last Updated: 2020-12-21
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
60 participants
INTERVENTIONAL
2012-04-20
2016-07-29
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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STI571 (imatinib mesylate) and BKM120
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.
STI571
STI571+BKM120
BKM120 Monotherapy 8 day run-in followed by STI571 and BKM120 combination therapy
STI571
BKM120
BKM120 combination therapy
STI571 monotherapy run-in
STI571 Monotherapy 8 day run-in followed by STI571 and BKM120 combination therapy
STI571
Interventions
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STI571
BKM120
BKM120 combination therapy
Eligibility Criteria
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Inclusion Criteria
2. WHO performance status (PS) of 0-2
3. Histologically confirmed diagnosis of GIST that is unresectable or metastatic
4. 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.
5. 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
Exclusion Criteria
2. 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
3. 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
* 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)
4. 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).
5. Poorly controlled diabetes mellitus (defined as HbA1c \> 8%)
18 Years
ALL
No
Sponsors
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Novartis Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Novartis Pharmaceuticals
Role: STUDY_DIRECTOR
Novartis Pharmaceuticals
Locations
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Dana Farber Cancer Institute SC (2)
Boston, Massachusetts, United States
Seattle Cancer Care Alliance Onc
Seattle, Washington, United States
Novartis Investigative Site
Leuven, , Belgium
Novartis Investigative Site
Vancouver, British Columbia, Canada
Novartis Investigative Site
Lyon, , France
Novartis Investigative Site
Villejuif, , France
Novartis Investigative Site
Kashiwa, Chiba, Japan
Novartis Investigative Site
Leiden, , Netherlands
Novartis Investigative Site
Barcelona, Catalonia, Spain
Novartis Investigative Site
London, , United Kingdom
Novartis Investigative Site
Manchester, , United Kingdom
Countries
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References
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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.
Related Links
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Novartis' results database
Other Identifiers
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2011-002938-39
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CSTI571X2101
Identifier Type: -
Identifier Source: org_study_id