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:	Novartis
ClinicalTrials.gov Identifier:	NCT00620594

Purpose

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

Phase I dose escalation part (advanced solid tumors):

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 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 and efficacy expansion parts of the trial will be opened for enrollment.

Phase I safety expansion part (advanced solid tumors):

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

Phase II expansion part (advanced breast cancer):

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

An effort will be made to enrich the trial population with Cowden Syndrome patients with advanced solid malignancies.

Condition	Intervention	Phase
Solid Tumors Breast Cancer	Drug: BEZ235	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
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

MedlinePlus related topics: Breast Cancer Cancer

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Maximum Tolerated Dose (MTD) of BEZ235 (Phase I dose escalation) [ Time Frame: at end of study - October 2010 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pharmacokinetics which includes AUC, Cmax, Tmax, t1/2 as endpoints [ Time Frame: at end of study - October 2010 ] [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	December 2006
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
BEZ235 alone: Experimental Dose Escalation	Drug: BEZ235
BEZ235 + trastuzumab: Experimental Dose Escalation	Drug: BEZ235
BEZ235: Experimental 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 Dose Escalation arm]: Female patients with histologically confirmed, 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 pre-screened for molecular alterations affecting PIK3CA and/or PTEN. Patients with NSCLC will be pre-screened for EGFR mutation.

Age ≥ 18

Exclusion Criteria:

-Patients who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases.

Prior treatment with a PI3K inhibitor-Acute or chronic liver disease or renal disease Acute or chronic pancreatitis Patients with any peripheral neuropathy ≥ CTCAE grade 2 Patients with unresolved diarrhea ≥ CTCAE grade 2

Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:

Impaired cardiac function or clinically significant cardiac diseases
Patients with diabetes mellitus requiring insulin treatment, history of gestational diabetes mellitus
Patients with known coagulopathies (as per amendment 4)
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 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 protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

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

Contacts

Contact: Novartis

862 778 8300

Locations

United States, California
UCLA	Not yet recruiting
Los Angeles, California, United States, 90095
Principal Investigator: Carolyn Britten, M.D.
United States, Connecticut
Yale Medica Oncology	Not yet recruiting
New Haven, Connecticut, United States, 06536
Principal Investigator: Maysa Abu-Khalaf, M.D.
United States, Massachusetts
Dana Faber Cancer Institute	Not yet 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, 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
MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Roy Herbst, M.D.
Spain
Novartis Investigative Site	Recruiting
Barcelona, Spain
United Kingdom
Novartis Investigative Site	Not yet recruiting
Manchester, United Kingdom

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis Pharmaceuticals ( External Affairs )
Study ID Numbers:	CBEZ235A2101
Study First Received:	February 8, 2008
Last Updated:	November 18, 2009
ClinicalTrials.gov Identifier:	NCT00620594 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Novartis:

BEZ235A
Solid tumors
Breast cancer
Cowden Syndrome
Phosphatidylinositol 3'

kinase
PI3K inhibitor
sporadic
Advanced

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Skin Diseases
Breast Neoplasms
Breast Diseases

ClinicalTrials.gov processed this record on November 30, 2009