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

NCT00620594 | Completed Phase 1

• 2 other identifiers: CBEZ235A21012006-004353-23
• Study Type: interventional
• Target: 183
• Locations: 5 countries
• Sites: 15

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.

Conditions

Breast Cancer; Advanced Solid Tumors; Cowden Syndrome

Keywords

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

Outcome Measures

Primary Outcomes (2)

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

  at end of study

• 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)

  at end of study

Secondary Outcomes (3)

• assess the safety and tolerability of the various formulations of BEZ235

  at end of study

• Asses the Pharmacokinetics of BEZ235 which includes AUC, Cmax, Tmax, t1/2 as endpoints

  at end of study

• Preliminary anti-tumor activity (tumor response) of BEZ235 SDS as single agent and in combination with trastuzumab

  end of study

Study Arms (4)

BEZ235 Alone, Dose Escalation

EXPERIMENTAL

Drug: BEZ235

BEZ235 + trastuzumab, Dose Escalation

EXPERIMENTAL

Drug: BEZ235

BEZ235 Alone, MTD Expansion

EXPERIMENTAL

Drug: BEZ235

BEZ235 + Trastuzumab, MTD Expansion

EXPERIMENTAL

Drug: BEZ235

Interventions

BEZ235 DRUG

BEZ235 + Trastuzumab, MTD Expansion; BEZ235 + trastuzumab, Dose Escalation; BEZ235 Alone, Dose Escalation; BEZ235 Alone, MTD Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \[Single agent dose escalation arm\]: 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

University of California at Los Angeles JonssonComprehensiveCancerCtr

Los Angeles, California, 90095, United States

Location

Yale University School of Medicine YaleCancerCtr-ClinTrialsOffice

New Haven, Connecticut, 06520, United States

Location

Dana Farber Cancer Institute Clinical Trials ProjectManager

Boston, Massachusetts, 02215, United States

Location

Nevada Cancer Institute NVCC - Huntsman

Las Vegas, Nevada, 89135, United States

Location

Cancer Centers of the Carolinas CCC Faris

Greenville, South Carolina, 29605, United States

Location

Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(2)

Nashville, Tennessee, 37203, United States

Location

Baylor Health Care System/Sammons Cancer Center Baylor- Sammons

Dallas, Texas, 75246, United States

Location

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

Houston, Texas, 77030-4009, United States

Location

Tyler Cancer Center TCC

Tyler, Texas, 75702, United States

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46009, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Novartis Investigative Site

Manchester, M20 9BX, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms; Hamartoma Syndrome, Multiple; Neoplasms; Breast Diseases

Interventions

dactolisib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Hamartoma; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2008
• First Posted: February 21, 2008
• Study Start: December 21, 2006
• Primary Completion: January 8, 2013
• Study Completion: January 8, 2013
• Last Updated: December 9, 2020

Record last verified: 2017-02

Locations

ES (3); US (9); NL (1); DE (1); GB (1)