Overview

This trial has been completed.

Condition 3rd line gist
Treatments sti571, bkm120
Phase phase 1
Sponsor Novartis Pharmaceuticals
Start date April 2012
End date July 2016
Trial size 60 participants
Trial identifier NCT01468688, 2011-002938-39, CSTI571X2101

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(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.
sti571
(Experimental)
BKM120 Monotherapy 8 day run-in followed by STI571 and BKM120 combination therapy
sti571
bkm120
BKM120 combination therapy
(Experimental)
STI571 Monotherapy 8 day run-in followed by STI571 and BKM120 combination therapy
sti571

Primary Outcomes

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)

Secondary Outcomes

Measure
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)

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Novartis.