A Phase I/II Study of BEZ235 in Patients With Advanced Solid Malignancies Enriched by Patients With Advanced Breast Cancer
- Conditions
- Advanced Solid TumorsBreast CancerCowden Syndrome
- Interventions
- Registration Number
- NCT00620594
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 183
[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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BEZ235 + trastuzumab, Dose Escalation BEZ235 - BEZ235 Alone, MTD Expansion BEZ235 - BEZ235 Alone, Dose Escalation BEZ235 - BEZ235 + Trastuzumab, MTD Expansion BEZ235 -
- Primary Outcome Measures
Name Time Method determine the maximum Tolerated Dose (MTD) of BEZ235 as single agent and in combination with trastuzumab (Dose escalation part) at end of study assess the safety & tolerability of BEZ235 SDS as single agent and in combination with trastuzumab administered to patients at the MTD level (Safety expansion part) at end of study
- Secondary Outcome Measures
Name Time Method Preliminary anti-tumor activity (tumor response) of BEZ235 SDS as single agent and in combination with trastuzumab end of study Asses the Pharmacokinetics of BEZ235 which includes AUC, Cmax, Tmax, t1/2 as endpoints at end of study assess the safety and tolerability of the various formulations of BEZ235 at end of study
Trial Locations
- Locations (10)
Yale University School of Medicine YaleCancerCtr-ClinTrialsOffice
🇺🇸New Haven, Connecticut, United States
University of California at Los Angeles JonssonComprehensiveCancerCtr
🇺🇸Los Angeles, California, United States
Novartis Investigative Site
🇬🇧Manchester, United Kingdom
Tyler Cancer Center TCC
🇺🇸Tyler, Texas, United States
Baylor Health Care System/Sammons Cancer Center Baylor- Sammons
🇺🇸Dallas, Texas, United States
Dana Farber Cancer Institute Clinical Trials ProjectManager
🇺🇸Boston, Massachusetts, United States
Nevada Cancer Institute NVCC - Huntsman
🇺🇸Las Vegas, Nevada, United States
University of Texas/MD Anderson Cancer Center Thoractic Head/Neck Med.Onc(2)
🇺🇸Houston, Texas, United States
Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(2)
🇺🇸Nashville, Tennessee, United States
Cancer Centers of the Carolinas CCC Faris
🇺🇸Greenville, South Carolina, United States