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