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

Primary Purpose

Breast Cancer, Advanced Solid Tumors, Cowden Syndrome

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BEZ235
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Neoplasms, breast neoplasms, breast diseases, solid tumors, BEZ235, breast cancer, PI3K Inhibitor, Phosphatidylinositol 3, kinase, advanced

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California at Los Angeles JonssonComprehensiveCancerCtr
  • Yale University School of Medicine YaleCancerCtr-ClinTrialsOffice
  • Dana Farber Cancer Institute Clinical Trials ProjectManager
  • Nevada Cancer Institute NVCC - Huntsman
  • Cancer Centers of the Carolinas CCC Faris
  • Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(2)
  • Baylor Health Care System/Sammons Cancer Center Baylor- Sammons
  • University of Texas/MD Anderson Cancer Center Thoractic Head/Neck Med.Onc(2)
  • Tyler Cancer Center TCC
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

BEZ235 Alone, Dose Escalation

BEZ235 + trastuzumab, Dose Escalation

BEZ235 Alone, MTD Expansion

BEZ235 + Trastuzumab, MTD Expansion

Arm Description

Outcomes

Primary Outcome Measures

determine the maximum Tolerated Dose (MTD) of BEZ235 as single agent and in combination with trastuzumab (Dose escalation part)
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)

Secondary Outcome Measures

assess the safety and tolerability of the various formulations of BEZ235
Asses the Pharmacokinetics of BEZ235 which includes AUC, Cmax, Tmax, t1/2 as endpoints
Preliminary anti-tumor activity (tumor response) of BEZ235 SDS as single agent and in combination with trastuzumab

Full Information

First Posted
February 8, 2008
Last Updated
December 6, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00620594
Brief Title
A Phase I/II Study of BEZ235 in Patients With Advanced Solid Malignancies Enriched by Patients With Advanced Breast Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
December 21, 2006 (Actual)
Primary Completion Date
January 8, 2013 (Actual)
Study Completion Date
January 8, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Advanced Solid Tumors, Cowden Syndrome
Keywords
Neoplasms, breast neoplasms, breast diseases, solid tumors, BEZ235, breast cancer, PI3K Inhibitor, Phosphatidylinositol 3, kinase, advanced

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
183 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BEZ235 Alone, Dose Escalation
Arm Type
Experimental
Arm Title
BEZ235 + trastuzumab, Dose Escalation
Arm Type
Experimental
Arm Title
BEZ235 Alone, MTD Expansion
Arm Type
Experimental
Arm Title
BEZ235 + Trastuzumab, MTD Expansion
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
BEZ235
Primary Outcome Measure Information:
Title
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
Title
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
Secondary Outcome Measure Information:
Title
assess the safety and tolerability of the various formulations of BEZ235
Time Frame
at end of study
Title
Asses the Pharmacokinetics of BEZ235 which includes AUC, Cmax, Tmax, t1/2 as endpoints
Time Frame
at end of study
Title
Preliminary anti-tumor activity (tumor response) of BEZ235 SDS as single agent and in combination with trastuzumab
Time Frame
end of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of California at Los Angeles JonssonComprehensiveCancerCtr
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Yale University School of Medicine YaleCancerCtr-ClinTrialsOffice
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Dana Farber Cancer Institute Clinical Trials ProjectManager
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Nevada Cancer Institute NVCC - Huntsman
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89135
Country
United States
Facility Name
Cancer Centers of the Carolinas CCC Faris
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(2)
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Baylor Health Care System/Sammons Cancer Center Baylor- Sammons
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
University of Texas/MD Anderson Cancer Center Thoractic Head/Neck Med.Onc(2)
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
Tyler Cancer Center TCC
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46009
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46010
Country
Spain
Facility Name
Novartis Investigative Site
City
Manchester
ZIP/Postal Code
M20 9BX
Country
United Kingdom

12. IPD Sharing Statement

Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=10543
Description
Results for CBEZ235A2101 can be found on the Novartis Clinical Trial Results Website

Learn more about this trial

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

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