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NCT Number: NCT00620594

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

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.

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Key information

Conditions

Breast Cancer Advanced Solid Tumors Breast Diseases Breast Neoplasms Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cowden Syndrome Genetic Diseases, Inborn Hamartoma Hamartoma Syndrome, Multiple Neoplasms Neoplasms by Site Neoplasms, Multiple Primary Neoplastic Syndromes, Hereditary Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Essen, Germany

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

BEZ235

Drug

Primary outcomes

  1. 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

  2. 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 outcomes

  1. assess the safety and tolerability of the various formulations of BEZ235

    Time frame: at end of study

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

    Time frame: at end of study

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

    Time frame: end of study

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2006
Primary completion
2013
Study completion
2013
First posted
Feb 21, 2008
Registry last updated
Dec 9, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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