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

Sponsor:	Novartis Pharmaceuticals
Information provided by (Responsible Party):	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00620594

Purpose

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.

Condition	Intervention	Phase
Breast Cancer, Advanced Solid Tumors, Cowden Syndrome	Drug: BEZ235	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer Cowden syndrome Help Me Understand Genetics

MedlinePlus related topics: Breast Cancer Cancer

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

determine the maximum Tolerated Dose (MTD) of BEZ235 as single agent and in combination with trastuzumab (Dose escalation part) [ Time Frame: at end of study ] [ Designated as safety issue: Yes ]
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) [ Time Frame: at end of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

assess the safety and tolerability of the various formulations of BEZ235 [ Time Frame: at end of study ] [ Designated as safety issue: Yes ]
Asses the Pharmacokinetics of BEZ235 which includes AUC, Cmax, Tmax, t1/2 as endpoints [ Time Frame: at end of study ] [ Designated as safety issue: No ]
Preliminary anti-tumor activity (tumor response) of BEZ235 SDS as single agent and in combination with trastuzumab [ Time Frame: end of study ] [ Designated as safety issue: No ]

Estimated Enrollment:	187
Study Start Date:	December 2006
Estimated Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BEZ235 Alone, Dose Escalation	Drug: BEZ235
Experimental: BEZ235 + trastuzumab, Dose Escalation	Drug: BEZ235
Experimental: BEZ235 Alone, MTD Expansion	Drug: BEZ235
Experimental: BEZ235 + Trastuzumab, MTD Expansion	Drug: BEZ235

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00620594

Contacts

Contact: Novartis Pharmaceuticals

800-340-6843

Locations

United States, California
UCLA	Recruiting
Los Angeles, California, United States, 90095
Principal Investigator: Carolyn Britten, M.D.
United States, Connecticut
Smilow Cancer Hospital of Yale New Haven	Recruiting
New Haven, Connecticut, United States, 06520
Contact: Maysa Abu-Khalaf, M.D.
Principal Investigator: Maysa Abu-Khalaf, M.D.
United States, Massachusetts
Dana Faber Cancer Institute/ Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Ian Krop, M.D.
United States, Nevada
Nevada Cancer Institute	Recruiting
Las Vegas, Nevada, United States, 89135
Principal Investigator: Lin C Chen, M.D.
United States, South Carolina
Cancer Center of the Carolinas	Recruiting
Greenville, South Carolina, United States, 29605
Contact: Joe Stephenson, M.D.
Principal Investigator: Joe Stephenson, M.D.
United States, Tennessee
Sarah Cannon Research Institute	Recruiting
Nashville, Tennessee, United States, 37203
Contact: Howard Burris, M.D. 615-329-7224
Principal Investigator: Howard Burris, M.D.
United States, Texas
Texas Oncology Sammons Cancer Center	Recruiting
Dallas, Texas, United States, 75246
Contact: Carlos Becerra, M.D.
Principal Investigator: Carlos Becerra, M.D.
MD Anderson Cancer Center	Suspended
Houston, Texas, United States, 77030
Tyler Cancer Center	Recruiting
Tyler, Texas, United States, 75702
Contact: Donald Richards, M.D.
Principal Investigator: Donald Richards, M.D.
United States, Washington
Northwest Cancer Specialists	Active, not recruiting
Vancouver, Washington, United States, 98684
Germany
Novartis Investigative Site	Recruiting
Essen, Germany
Netherlands
Novartis Investigative Site	Recruiting
Amsterdam, Netherlands
Spain
Novartis Investigative Site	Recruiting
Barcelona, Spain
Novartis Investigative Site	Recruiting
Madrid, Spain
Novartis Investigative Site	Recruiting
Valencia, Spain
United Kingdom
Novartis Investigative Site	Recruiting
Manchester, United Kingdom

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00620594 History of Changes
Other Study ID Numbers:	CBEZ235A2101, EudraCT 2006-004353-23
Study First Received:	February 8, 2008
Last Updated:	November 17, 2011
Health Authority:	United States: Food and Drug Administration; Germany: BfArM (The Federal Institute for Drugs and Medical Devices); Netherlands: Dutch Health Care Inspectorate; Spain: Agencia Espanola del Medicamento y Productos Sanitarios; United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:

Neoplasms,
breast neoplasms,
breast diseases,
solid tumors,
BEZ235,

breast cancer,
PI3K Inhibitor,
Phosphatidylinositol 3',
kinase,
advanced

Additional relevant MeSH terms:

Breast Neoplasms
Hamartoma Syndrome, Multiple
Neoplasms by Site
Neoplasms
Breast Diseases

Skin Diseases
Hamartoma
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on February 09, 2012