NCT00620594

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

Completed Phase 1 Last updated 9 December 2020

What this trial tests

Phase 1 trial testing BEZ235 in Breast Cancer in 183 participants. Completed in 8 January 2013.

Timeline

21 December 2006

Primary endpoint
8 January 2013

8 January 2013

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	183
Start date	21 December 2006
Primary completion	8 January 2013
Estimated completion	8 January 2013
Sites	15 locations across Netherlands, United Kingdom, Germany, United States, Spain

Drugs / interventions tested

• BEZ235 — full drug profile →

Conditions studied

• Breast Cancer — all drugs for Breast Cancer →
• Advanced Solid Tumors — all drugs for Advanced Solid Tumors →
• Cowden Syndrome — all drugs for Cowden Syndrome →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Breast Cancer or Advanced Solid Tumors. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.
   Panwar V, Singh A, Bhatt M, Tonk RK, et al · · 2023 · cited 628× · PMID 37779156 · DOI 10.1038/s41392-023-01608-z
2. Role of PI3K/AKT pathway in cancer: the framework of malignant behavior.
   Jiang N, Dai Q, Su X, Fu J, et al · · 2020 · cited 419× · PMID 32333246 · DOI 10.1007/s11033-020-05435-1
3. CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors.
   Vora SR, Juric D, Kim N, Mino-Kenudson M, et al · · 2014 · cited 361× · PMID 25002028 · DOI 10.1016/j.ccr.2014.05.020
4. Acquisition of epithelial-mesenchymal transition and cancer stem cell phenotypes is associated with activation of the PI3K/Akt/mTOR pathway in prostate cancer radioresistance.
   Chang L, Graham PH, Hao J, Ni J, et al · · 2013 · cited 298× · PMID 24157869 · DOI 10.1038/cddis.2013.407
5. Targeting the PI3K/Akt/mTOR pathway--beyond rapalogs.
   Markman B, Dienstmann R, Tabernero J. · · 2010 · cited 262× · PMID 21317449 · DOI 10.18632/oncotarget.188
6. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: how mutations can result in therapy resistance and how to overcome resistance.
   McCubrey JA, Steelman LS, Chappell WH, Abrams SL, et al · · 2012 · cited 242× · PMID 23085539 · DOI 10.18632/oncotarget.659
7. Role of the PI3K/AKT and mTOR signaling pathways in acute myeloid leukemia.
   Park S, Chapuis N, Tamburini J, Bardet V, et al · · 2010 · cited 229× · PMID 19951971 · DOI 10.3324/haematol.2009.013797
8. Therapeutic targeting of cancers with loss of PTEN function.
   Dillon LM, Miller TW. · · 2014 · cited 194× · PMID 24387334 · DOI 10.2174/1389450114666140106100909