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

Metastatic or Locally Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01285466
• Other study ID #: CBEZ235A2118
• Secondary ID: 2010-022331-11
• Status: Completed
• Phase: Phase 1
• Start date: January 2011
• Est. completion date: October 2014

Study information

• Verified date: February 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastatic or Locally Advanced Solid Tumors

Intervention

Drug:
• BEZ235 + paclitaxel

• BKM120 + paclitaxel

• BEZ235 + paclitaxel + trastuzumab

• BKM120 + paclitaxel + trastuzumab

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Wilrijk
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Köln
Netherlands	Novartis Investigative Site	Amsterdam
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Sevilla	Andalucia
Switzerland	Novartis Investigative Site	Chur
Switzerland	Novartis Investigative Site	St. Gallen

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  Germany,  Netherlands,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose limiting toxicities during the first cycle of treatment.		First treatment cycle (4 weeks)
Secondary	Incidence of safety events during the whole treatment period (until progression of disease).		From start of treatment until disease progression
Secondary	pharmacokinetics of BEZ235, BKM120 and paclitaxel given in combination, on Day 1, 8 and 22.		First treatment cycle (4 weeks)
Secondary	Treatment efficacy (response to treatment according to RECIST criteria)		From start of treatment until disease progression
Secondary	Impact of treatment on biomarkers of Pi3 Kinase pathway (analyses of skin biopsies, circulating markers)		From start of treatment until disease progression

External Links

•   Results for CBEZ235A2118 can be found on the Novartis Clinical Trials website