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

Completed · Phase 1

Conditions studied: Breast Cancer, Advanced Solid Tumors, Cowden Syndrome

In brief

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.

Key facts

Study ID: NCT00620594
Run by: Novartis Pharmaceuticals
People needed: 183
Starts: 2006-12-21
Expected to finish: 2013-01-08
Last updated by the study team: 2020-12-09

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

[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.

You may not qualify if…

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

Where it is running

University of California at Los Angeles JonssonComprehensiveCancerCtr — Los Angeles, California, United States
Yale University School of Medicine YaleCancerCtr-ClinTrialsOffice — New Haven, Connecticut, United States
Dana Farber Cancer Institute Clinical Trials ProjectManager — Boston, Massachusetts, United States
Nevada Cancer Institute NVCC - Huntsman — Las Vegas, Nevada, United States
Cancer Centers of the Carolinas CCC Faris — Greenville, South Carolina, United States
Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(2) — Nashville, Tennessee, United States
Baylor Health Care System/Sammons Cancer Center Baylor- Sammons — Dallas, Texas, United States
University of Texas/MD Anderson Cancer Center Thoractic Head/Neck Med.Onc(2) — Houston, Texas, United States
Tyler Cancer Center TCC — Tyler, Texas, United States
Novartis Investigative Site — Essen, Germany
Novartis Investigative Site — Amsterdam, Netherlands
Novartis Investigative Site — Barcelona, Catalonia, Spain
Novartis Investigative Site — Valencia, Valencia, Spain
Novartis Investigative Site — Valencia, Valencia, Spain
Novartis Investigative Site — Manchester, United Kingdom

Full record on ClinicalTrials.gov

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