A Phase I/II Study of BEZ235 in Patients With Advanced Solid Malignancies Enriched by Patients With Advanced Breast Cancer

Status:	Completed
Conditions:	Breast Cancer, Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	2/15/2017
Start Date:	December 21, 2006
End Date:	January 8, 2013

A Phase I/II, Multi-center, Open-label Study of BEZ235, Administered Orally on a Continuous Daily Dosing Schedule in Adult Patients With Advanced Solid Malignancies Including Patients With Advanced Breast Cancer

This is a first-in-human, phase I/Ib clinical research study with BEZ235, an inhibitor of
phosphatidylinositol 3'-kinase (PI3K). The study consists of a dose escalation part followed
by a safety dose expansion part:

Dose escalation part (advanced solid tumors, including patients with breast cancer being
treated with trastuzumab):

Patients receive oral BEZ235 once daily on days 1-28 of the first course. Courses will
repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of at least 3 patients receive escalating doses of BEZ235, as single agent or in
combination with trastuzumab, until the maximum tolerated dose (MTD) is determined. The MTD
is defined as the dose expected to produce during the first course of treatment
dose-limiting toxicity in 33% of patients.

Once the MTD has been defined, the safety expansion parts of the trial will be opened for
enrollment.

Safety dose expansion part (advanced solid tumors, including patients with breast cancer
being treated with trastuzumab):

Patients will be treated with BEZ235, as single agent or in combination with trastuzumab,
given at the MTD, once daily. Treatment of patients will continue until disease progression
or occurrence of unacceptable side effects.

Inclusion Criteria:

[Single agent dose escalation arm]: Patients with histologically-confirmed, advanced
unresectable solid tumors including CS patients who have progressed on (or not been able
to tolerate) standard therapy within three months before screening visit or for whom no
standard anticancer therapy exists.

[Combination part]: Patients with metastatic HER2+ Breast Cancer, after failure of
trastuzumab treatment. Eligible patients will have to have tumors carrying molecular
alterations of PIK3CA and/or PTEN.

[Single agent safety expansion arm]: Patients with histologically-confirmed, advanced
unresectable solid tumors including CS patients who have progressed on (or not been able
to tolerate) standard therapy within three months before screening visit or for whom no
standard anticancer therapy exists. Patients will be prescreened for molecular alterations
affecting PIK3CA and/or PTEN. Patients with NSCLC will also be pre-screened for EGFR
mutation.

Exclusion Criteria:

- Patients who have brain metastases, which are progressive and/or requiring medical
intervention for symptom control

- Prior treatment with a PI3K inhibitor

- Acute or chronic liver disease or renal disease

- Acute or chronic pancreatitis

- Patients with unresolved diarrhea ≥ CTCAE grade 2

- Impaired cardiac function or clinically significant cardiac diseases

- Patients with diabetes mellitus requiring insulin treatment

- Patients with known coagulopathies

- Patients with a history of photosensitivity reactions to other drugs

- Any of the following ophthalmological findings:

- Progressive eye disease that could lead to severe loss of visual acuity or visual
field

- loss during the study period

- Inability to perform the ophthalmic procedures required in this protocol

- Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.
active or uncontrolled infection) that could cause unacceptable safety risks or
compromise compliance with the protocol.

Other protocol-defined inclusion/exclusion criteria may apply

We found this trial at

sites

Dana Farber Cancer Institute Clinical Trials ProjectManager

450 Brookline Avenue
Boston, Massachusetts 02215

from

Boston, MA