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

NCT ID: NCT00620594

Last Updated: 2020-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

183 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-12-21

Study Completion Date

2013-01-08

Brief Summary

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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

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Conditions

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Breast Cancer Advanced Solid Tumors Cowden Syndrome

Keywords

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Neoplasms breast neoplasms breast diseases solid tumors BEZ235 breast cancer PI3K Inhibitor Phosphatidylinositol 3 kinase advanced

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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BEZ235 Alone, Dose Escalation

Group Type EXPERIMENTAL

BEZ235

Intervention Type DRUG

BEZ235 + trastuzumab, Dose Escalation

Group Type EXPERIMENTAL

BEZ235

Intervention Type DRUG

BEZ235 Alone, MTD Expansion

Group Type EXPERIMENTAL

BEZ235

Intervention Type DRUG

BEZ235 + Trastuzumab, MTD Expansion

Group Type EXPERIMENTAL

BEZ235

Intervention Type DRUG

Interventions

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BEZ235

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University of California at Los Angeles JonssonComprehensiveCancerCtr

Los Angeles, California, United States

Site Status

Yale University School of Medicine YaleCancerCtr-ClinTrialsOffice

New Haven, Connecticut, United States

Site Status

Dana Farber Cancer Institute Clinical Trials ProjectManager

Boston, Massachusetts, United States

Site Status

Nevada Cancer Institute NVCC - Huntsman

Las Vegas, Nevada, United States

Site Status

Cancer Centers of the Carolinas CCC Faris

Greenville, South Carolina, United States

Site Status

Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(2)

Nashville, Tennessee, United States

Site Status

Baylor Health Care System/Sammons Cancer Center Baylor- Sammons

Dallas, Texas, United States

Site Status

University of Texas/MD Anderson Cancer Center Thoractic Head/Neck Med.Onc(2)

Houston, Texas, United States

Site Status

Tyler Cancer Center TCC

Tyler, Texas, United States

Site Status

Novartis Investigative Site

Essen, , Germany

Site Status

Novartis Investigative Site

Amsterdam, , Netherlands

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Valencia, Valencia, Spain

Site Status

Novartis Investigative Site

Valencia, Valencia, Spain

Site Status

Novartis Investigative Site

Manchester, , United Kingdom

Site Status

Countries

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United States Germany Netherlands Spain United Kingdom

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=10543

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

Other Identifiers

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2006-004353-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBEZ235A2101

Identifier Type: -

Identifier Source: org_study_id