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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00620594
First received: February 8, 2008
Last updated: November 19, 2013
Last verified: November 2013
  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 1

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:


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 ]

Enrollment: 183
Study Start Date: December 2006
Study Completion Date: January 2013
Primary Completion Date: January 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
University of California at Los Angeles JonssonComprehensiveCancerCtr
Los Angeles, California, United States, 90095
United States, Connecticut
Yale University School of Medicine YaleCancerCtr-ClinTrialsOffice
New Haven, Connecticut, United States, 06520
United States, Massachusetts
Dana Farber Cancer Institute Clinical Trials ProjectManager
Boston, Massachusetts, United States, 02115
United States, Nevada
Nevada Cancer Institute NVCC - Huntsman
Las Vegas, Nevada, United States, 89135
United States, South Carolina
Cancer Centers of the Carolinas CCC Faris
Greenville, South Carolina, United States, 29605
United States, Tennessee
Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(2)
Nashville, Tennessee, United States, 37203
United States, Texas
Baylor Health Care System/Sammons Cancer Center Baylor- Sammons
Dallas, Texas, United States, 75246
University of Texas/MD Anderson Cancer Center Thoractic Head/Neck Med.Onc(2)
Houston, Texas, United States, 77030-4009
Tyler Cancer Center TCC
Tyler, Texas, United States, 75702
Germany
Novartis Investigative Site
Essen, Germany, 45147
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1066 CX
Spain
Novartis Investigative Site
Barcelona, Cataluña, Spain, 08035
Novartis Investigative Site
Valencia, Comunidad Valenciana, Spain, 46010
Novartis Investigative Site
Valencia, Comunidad Valenciana, Spain, 46009
United Kingdom
Novartis Investigative Site
Manchester, United Kingdom, M20 9BX
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00620594     History of Changes
Other Study ID Numbers: CBEZ235A2101, 2006-004353-23
Study First Received: February 8, 2008
Last Updated: November 19, 2013
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
Breast Diseases
Genetic Diseases, Inborn
Hamartoma
Neoplasms
Neoplasms by Site
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Skin Diseases

ClinicalTrials.gov processed this record on October 23, 2014