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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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
3rd Line GIST

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Trial Information

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

Inclusion 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.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

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

Outcome Description:

Dose limiting toxicity (DLT) will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) (v4.0.3), unless otherwise specified in the protocol.

Outcome Time Frame:

28 days (1st cycle)

Safety Issue:

Yes

Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals

Authority:

United States: Food and Drug Administration

Study ID:

CSTI571X2101

NCT ID:

NCT01468688

Start Date:

April 2012

Completion Date:

September 2014

Related Keywords:

  • 3rd Line GIST
  • Imatinib mesylate
  • BKM120
  • GIST
  • Gastrointestinal Stromal Tumors

Name

Location

Dana Farber Cancer Institute SC (2)Boston, Massachusetts  02115
Memorial Sloan Kettering Cancer Center MSKCC SCNew York, New York  10021
Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research OncSeattle, Washington  98109-1023