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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00620594
• Other study ID #: CBEZ235A2101
• Secondary ID: 2006-004353-23
• Status: Completed
• Phase: Phase 1
• Start date: December 21, 2006
• Est. completion date: January 8, 2013

Study information

• Verified date: February 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 183
• Est. completion date: January 8, 2013
• Est. primary completion date: January 8, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Breast Cancer
• Breast Neoplasms
• Cowden Syndrome
• Hamartoma Syndrome, Multiple

Intervention

Drug:
• BEZ235

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	determine the maximum Tolerated Dose (MTD) of BEZ235 as single agent and in combination with trastuzumab (Dose escalation part)		at end of study
Primary	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	assess the safety and tolerability of the various formulations of BEZ235		at end of study
Secondary	Asses the Pharmacokinetics of BEZ235 which includes AUC, Cmax, Tmax, t1/2 as endpoints		at end of study
Secondary	Preliminary anti-tumor activity (tumor response) of BEZ235 SDS as single agent and in combination with trastuzumab		end of study

External Links

•   Results for CBEZ235A2101 can be found on the Novartis Clinical Trial Results Website