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

3rd Line GIST Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01468688
• Other study ID #: CSTI571X2101
• Secondary ID: 2011-002938-39
• Status: Completed
• Phase: Phase 1
• Start date: April 20, 2012
• Est. completion date: July 29, 2016

Study information

• Verified date: September 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: July 29, 2016
• Est. primary completion date: July 29, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• 3rd Line GIST
• Gastrointestinal Stromal Tumors

Intervention

Drug:
• STI571

• BKM120
BKM120 combination therapy

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Vancouver	British Columbia
France	Novartis Investigative Site	Lyon Cedex
France	Novartis Investigative Site	Villejuif Cedex
Japan	Novartis Investigative Site	Kashiwa	Chiba
Netherlands	Novartis Investigative Site	Leiden
Spain	Novartis Investigative Site	Barcelona	Catalunya
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United States	Dana Farber Cancer Institute SC (2)	Boston	Massachusetts
United States	Seattle Cancer Care Alliance Onc	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Japan,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	28 days (1st cycle)
Secondary	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.	28 days (1st cycle)
Secondary	Imatinib and BKM120 plasma concentrations vs time profile, and basic PK parameters, including but not limited to AUC, Cmax, Tmax, CL/F.		28 days (1st cycle)
Secondary	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.	28 days (1st cycle)

External Links

•   Novartis' results database