Clinical trial NCT01285466: A Trial of Oral BEZ235 and BKM120 in Combination With Paclitaxel With or Without Trastuzumab
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic or Locally Advanced Solid Tumors
Keywords: Cancer
BEZ235
BKM120
paclitaxel
trastuzumab
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-01-28
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Incidence of Dose limiting toxicities during the first cycle of treatment.
timeFrame: First treatment cycle (4 weeks)
Secondary outcomes:
measure: Incidence of safety events during the whole treatment period (until progression of disease).
timeFrame: From start of treatment until disease progression
measure: pharmacokinetics of BEZ235, BKM120 and paclitaxel given in combination, on Day 1, 8 and 22.
timeFrame: First treatment cycle (4 weeks)
measure: Treatment efficacy (response to treatment according to RECIST criteria)
timeFrame: From start of treatment until disease progression
measure: Impact of treatment on biomarkers of Pi3 Kinase pathway (analyses of skin biopsies, circulating markers)
timeFrame: From start of treatment until disease progression
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Wilrijk
country: Belgium
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Köln
country: Germany
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Chur
country: Switzerland
facility: Novartis Investigative Site
city: St. Gallen
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: