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A Dose-finding Study of a Combination of Imatinib and BKM120 in the Treatment of 3rd Line GIST Patients

Information source: Novartis
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: 3rd Line GIST

Intervention: STI571 + BKM120 (Drug); STI571 + BKM120 (Drug); STI571 + BKM120 (Drug)

Phase: Phase 1

Status: Active, not recruiting

Sponsored by: Novartis Pharmaceuticals

Official(s) and/or principal investigator(s):
Novartis Pharmaceuticals, Study Director, Affiliation: Novartis Pharmaceuticals


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.

Clinical Details

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

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Frequency and characteristics of dose limiting toxicities (DLTs) at each dose level during the first cycle of therapy

Secondary outcome:

Frequency and characteristics of DLTs at each dose level during the first cycle of therapy. Type, frequency and severity of adverse drug reactions.

Imatinib and BKM120 plasma concentrations vs time profile, and basic PK parameters, including but not limited to AUC, Cmax, Tmax, CL/F.

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.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion criteria: 1. Male or female patients ≥ 18 years of age 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: 1. Previous treatment with PI3-K inhibitors 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%) Other protocol-defined inclusion/exclusion criteria may apply.

Locations and Contacts

Novartis Investigative Site, Leuven 3000, Belgium

Novartis Investigative Site, Lyon Cedex 69373, France

Novartis Investigative Site, Villejuif Cedex 94805, France

Novartis Investigative Site, Leiden 2300 RC, Netherlands

Novartis Investigative Site, London SW3 6JJ, United Kingdom

Novartis Investigative Site, Manchester M20 9BX, United Kingdom

Novartis Investigative Site, Vancouver, British Columbia V5Z 4E6, Canada

Novartis Investigative Site, Barcelona, Catalunya 08035, Spain

Novartis Investigative Site, Kashiwa, Chiba 277-8577, Japan

Dana Farber Cancer Institute SC (2), Boston, Massachusetts 02115, United States

Seattle Cancer Care Alliance Onc, Seattle, Washington 98109-1023, United States

Additional Information

Starting date: April 2012
Last updated: January 6, 2015

Page last updated: August 23, 2015

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