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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01285466
First received: January 26, 2011
Last updated: January 15, 2014
Last verified: January 2014
  Purpose

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 Intervention 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
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence of Dose limiting toxicities during the first cycle of treatment. [ Time Frame: First treatment cycle (4 weeks) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of safety events during the whole treatment period (until progression of disease). [ Time Frame: From start of treatment until disease progression ] [ Designated as safety issue: Yes ]
  • pharmacokinetics of BEZ235, BKM120 and paclitaxel given in combination, on Day 1, 8 and 22. [ Time Frame: First treatment cycle (4 weeks) ] [ Designated as safety issue: No ]
  • Treatment efficacy (response to treatment according to RECIST criteria) [ Time Frame: From start of treatment until disease progression ] [ Designated as safety issue: No ]
  • Impact of treatment on biomarkers of Pi3 Kinase pathway (analyses of skin biopsies, circulating markers) [ Time Frame: From start of treatment until disease progression ] [ Designated as safety issue: No ]

Enrollment: 110
Study Start Date: January 2011
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01285466

Locations
Belgium
Novartis Investigative Site
Bruxelles, Belgium, 1000
Novartis Investigative Site
Bruxelles, Belgium, 1200
Novartis Investigative Site
Wilrijk, Belgium, 2610
Germany
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Köln, Germany, 50924
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1066 CX
Spain
Novartis Investigative Site
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site
Barcelona, Cataluña, Spain, 08035
Switzerland
Novartis Investigative Site
Chur, Switzerland, 7000
Novartis Investigative Site
St. Gallen, Switzerland, 9007
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: NCT01285466     History of Changes
Other Study ID Numbers: CBEZ235A2118, 2010-022331-11
Study First Received: January 26, 2011
Last Updated: January 15, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Ministry of Health
Germany:
Netherlands:
Spain:
Switzerland:

Keywords provided by Novartis:
Cancer,
BEZ235,
BKM120,
paclitaxel,
trastuzumab

Additional relevant MeSH terms:
Paclitaxel
Trastuzumab
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014