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

Phase 1

Completed

• Conditions: 3rd Line GIST
• Interventions: Drug: STI571; Drug: BKM120

• Registration Number: NCT01468688
• Lead Sponsor: Novartis Pharmaceuticals

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-11-06
• Study First Submitted QC: 2011-11-08
• Study First Posted: 2011-11-09
• Study Start: 2012-04-20
• Primary Completion: 2016-07-29
• Study Completion: 2016-07-29
• Status Verified: 2019-09
• Last Update Submitted: 2020-12-17
• Last Update Posted: 2020-12-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
STI571+BKM120	STI571	BKM120 Monotherapy 8 day run-in followed by STI571 and BKM120 combination therapy
STI571+BKM120	BKM120	BKM120 Monotherapy 8 day run-in followed by STI571 and BKM120 combination therapy
STI571 monotherapy run-in	STI571	STI571 Monotherapy 8 day run-in followed by STI571 and BKM120 combination therapy
STI571 (imatinib mesylate) and BKM120	STI571	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.

Primary Outcome Measures

Name	Time	Method
Frequency and characteristics of dose limiting toxicities (DLTs) at each dose level during the first cycle of therapy	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.

Secondary Outcome Measures

Name	Time	Method
Frequency and characteristics of DLTs at each dose level during the first cycle of therapy. Type, frequency and severity of adverse drug reactions.	28 days (1st cycle)	Dose limiting toxicity (DLT) will be assessed using CTCAE (v4.0.3), unless otherwise specified in the protocol.
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)
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.	28 days (1st cycle)	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.

Trial Locations

Locations (3)

Seattle Cancer Care Alliance Onc; 🇺🇸 Seattle, Washington, United States

Dana Farber Cancer Institute SC (2); 🇺🇸 Boston, Massachusetts, United States

Novartis Investigative Site; 🇬🇧 Manchester, United Kingdom