Phase Ib/II trial of BEZ235 with paclitaxel in patients with HER2 negative, locally advanced or metastatic breast cancer

• Conditions: Adult female patients with HER2 negative breast cancer which is found to be inoperable locally advanced or metastatic disease; MedDRA version: 14.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-002400-32-FR
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-10-21
• Last Update Posted: 4 August 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 230

Inclusion Criteria

Inclusion criteria applicable to Phase Ib and II:
•Patient is a female = 18 years of age.
•Patient has a histologically and/or cytologically confirmed diagnosis of breast cancer.
•Patient has radiological evidence of inoperable locally advanced or metastatic breast cancer.
•Patient has HER2 negative disease.
•Patient has adequate bone marrow and organ function.

Additional criteria for Phase II:
•Patient has a known PI3K status (activated or wildtype) based on results from a Novartis designated laboratory prior to start of treatment.
•Patient has recent radiological documentation of recurrent disease or newly diagnosed disease.
•Patient has at least one measurable lesion as per RECIST 1.1.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 170

Exclusion Criteria

Exclusion criteria applicable for Phase Ib and II:
•Patient has received previous treatment with PI3K and/or mTOR pathway inhibitors.
•Patient has active uncontrolled or symptomatic central nervous system (CNS) metastases.
•Patient has received wide field radiotherapy or irradiation of = 25% of the bone marrow = 28 days or limited field radiation for palliation = 14 days prior to starting study drug or has not recovered from side effects of such therapy.
•Patient has active cardiac disease or a history of cardiac dysfunction.
•Patient has a family history of congenital long or short QT, or known history of QT/QTc prolongation or Torsades de Pointes (TdP).
•Patient has inadequately controlled hypertension (i.e., SBP>180 mmHg or DBP>100mmHg).
•Patient has uncontrolled diabetes mellitus.
•Patient has impairment of GI function or GI disease that may significantly alter the absorption of BEZ235 and/ or paclitaxel.

Additional exclusion criterion for Phase II:
•Patient has received any prior chemotherapies for the inoperable locally advanced or metastatic disease.

Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: Phase Ib:<br>- to evaluate the safety of BEZ235 in combination with paclitaxel<br>- to assess the preliminary efficacy of the study treatment<br><br>Phase II:<br>- to estimate the treatment effect of BEZ235/paclitaxel combination therapy versus paclitaxel alone<br>- to estimate/compare the effect of study treatment<br>- to evaluate the safety and tolerability of the study treatment;Main Objective: Phase Ib:<br>to determine the MTD of BEZ235 in combination with paclitaxel<br><br>Phase II:<br>to estimate the treatment effect of BEZ235/paclitaxel combination therapy versus paclitaxel alone;Primary end point(s): Phase Ib:<br>DLTs (the first cycle) at each dose level<br><br>Phase II:<br>progression free survival according to local radiological assessment;Timepoint(s) of evaluation of this end point: Phase Ib:<br>after ~1 month treatment<br><br>Phase II: <br>throughout the study

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Phase Ib:<br>- 30-35 days after treatment discontinuation<br>- throughout the study <br><br>Phase II:<br>- throughout the study<br>- throughout the study<br>- 30-35 days after treatment discontinuation;Secondary end point(s): Phase Ib:<br>- frequency and severity of Adverse Events, abnormal laboratory values, other safety data as appropriate<br>- Progression Free Survival (PFS), Overall Response Rate (ORR), Clinical Benefit Rate<br><br>Phase II:<br>- Progression free survival in PI3K subgroups according to local radiological assessment<br>- Progression free survival (PFS) according to independent central radiological assessment, Clinical Benefit Rate, Time to Response, Duration of Response, Median Overall Survival, Overall Response Rate<br>- frequency and severity of Adverse Events, abnormal laboratory values, other safety data as appropriate