A Trial of Oral BEZ235 and BKM120 in Combination With Paclitaxel With or Without Trastuzumab

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01285466
Recruitment Status : Completed
First Posted : January 28, 2011
Last Update Posted : February 14, 2017
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of the trial is to determine the maximum tolerated dose (MTD) of BEZ235 and BKM120 in combination with weekly paclitaxel and weekly paclitaxel/trastuzumab.

Condition or disease Intervention/treatment Phase
Metastatic or Locally Advanced Solid Tumors Drug: BEZ235 + paclitaxel Drug: BKM120 + paclitaxel Drug: BEZ235 + paclitaxel + trastuzumab Drug: BKM120 + paclitaxel + trastuzumab Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 110 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib Multi-center, Open-label, 4-arm Dose-escalation Study of Oral BEZ235 and BKM120 in Combination With Weekly Paclitaxel in Patients With Advanced Solid Tumors and Weekly Paclitaxel/Trastuzumab in Patients With HER2+ Metastatic Breast Cancer
Study Start Date : January 2011
Actual Primary Completion Date : October 2014
Actual Study Completion Date : October 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: BEZ235 + paclitaxel Drug: BEZ235 + paclitaxel
Experimental: BKM120 + paclitaxel Drug: BKM120 + paclitaxel
Experimental: BEZ235 + paclitaxel + trastuzumab Drug: BEZ235 + paclitaxel + trastuzumab
Experimental: BKM120 + paclitaxel + trastuzumab Drug: BKM120 + paclitaxel + trastuzumab

Primary Outcome Measures :
  1. Incidence of Dose limiting toxicities during the first cycle of treatment. [ Time Frame: First treatment cycle (4 weeks) ]

Secondary Outcome Measures :
  1. Incidence of safety events during the whole treatment period (until progression of disease). [ Time Frame: From start of treatment until disease progression ]
  2. pharmacokinetics of BEZ235, BKM120 and paclitaxel given in combination, on Day 1, 8 and 22. [ Time Frame: First treatment cycle (4 weeks) ]
  3. Treatment efficacy (response to treatment according to RECIST criteria) [ Time Frame: From start of treatment until disease progression ]
  4. Impact of treatment on biomarkers of Pi3 Kinase pathway (analyses of skin biopsies, circulating markers) [ Time Frame: From start of treatment until disease progression ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Adult patients with metastatic or locally advanced solid tumors, for whom weekly paclitaxel treatment is indicated (BEZ235-paclitaxel /BKM120-paclitaxel treatment)
  • HER2+ metastatic or locally advanced breast cancer patients eligible for weekly paclitaxel and trastuzumab (BEZ235-paclitaxel-trastuzumab /BKM120-paclitaxel-trastuzumab treatment)
  • Adult patients (≥ 18 years) (males, females)
  • World Health Organization (WHO) performance status ≤ 2
  • Adequate bone marrow function:
  • Adequate hepatic and renal function:

Exclusion Criteria:

  • Patients with primary central nervous system (CNS) tumor or CNS tumor involvement. However, patients with a metastatic CNS lesion may participate in this trial, if the patient is > 4 weeks from therapy (including radiation and/or surgery) completion, clinically stable with respect to the tumor at the time of study entry, and not receiving enzyme-inducing antiepileptic drugs or corticosteroid therapy or taper, as treatment of the brain metastases
  • Patients who have received prior systemic anticancer therapy within the following time frames
  • Cyclical chemotherapy: ≤ 3 weeks before study treatment (6 weeks for patients treated with nitrosoureas)
  • Biological therapy: ≤ 4 weeks before study treatment, except treatment with trastuzumab (both parts of the trial)
  • Investigational drug: ≤ 4 weeks before study treatment
  • Patients who have undergone major surgery ≤ 4 weeks before study treatment
  • Patients receiving chronic treatment with corticosteroids or other immunosuppressive agents
  • Patients with uncontrolled, unmanageable, treatment-refractory diabetes mellitus
  • Active or history of major depressive episode, bipolar disorder, obsessive-compulsive disorder, schizophrenia, history of suicide attempt or ideation, or homicide, as judged by the investigator and/or based on recent psychiatric assessment

Other protocol-defined inclusion/exclusion criteria may apply

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01285466

Novartis Investigative Site
Bruxelles, Belgium, 1000
Novartis Investigative Site
Bruxelles, Belgium, 1200
Novartis Investigative Site
Wilrijk, Belgium, 2610
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Köln, Germany, 50937
Novartis Investigative Site
Amsterdam, Netherlands, 1066 CX
Novartis Investigative Site
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Chur, Switzerland, 7000
Novartis Investigative Site
St. Gallen, Switzerland, 9007
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals Identifier: NCT01285466     History of Changes
Other Study ID Numbers: CBEZ235A2118
2010-022331-11 ( EudraCT Number )
First Posted: January 28, 2011    Key Record Dates
Last Update Posted: February 14, 2017
Last Verified: February 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Additional relevant MeSH terms:
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action