E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult female patients with HER2 negative breast cancer which is found to be inoperable locally advanced or metastatic disease |
|
E.1.1.1 | Medical condition in easily understood language |
Inoperable locally advanced breast cancer,
Metastatic Breast Cancer (MBC)
|
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase Ib:
to determine the MTD of BEZ235 in combination with paclitaxel
Phase II:
to estimate the treatment effect of BEZ235/paclitaxel combination therapy versus paclitaxel alone |
|
E.2.2 | Secondary objectives of the trial |
Phase Ib:
- to evaluate the safety of BEZ235 in combination with paclitaxel
- to assess the preliminary efficacy of the study treatment
Phase II:
- to estimate the treatment effect of BEZ235/paclitaxel combination therapy versus paclitaxel alone
- to estimate/compare the effect of study treatment
- to evaluate the safety and tolerability of the study treatment |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
|
|
E.4 | Principal 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Phase Ib:
DLTs (the first cycle) at each dose level
Phase II:
progression free survival according to local radiological assessment |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase Ib:
after ~1 month treatment
Phase II:
throughout the study |
|
E.5.2 | Secondary end point(s) |
Phase Ib:
- frequency and severity of Adverse Events, abnormal laboratory values, other safety data as appropriate
- Progression Free Survival (PFS), Overall Response Rate (ORR), Clinical Benefit Rate
Phase II:
- Progression free survival in PI3K subgroups according to local radiological assessment
- 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
- frequency and severity of Adverse Events, abnormal laboratory values, other safety data as appropriate |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Phase Ib:
- 30-35 days after treatment discontinuation
- throughout the study
Phase II:
- throughout the study
- throughout the study
- 30-35 days after treatment discontinuation |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
dose escalation in combination with paclitaxel |
|
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Belgium |
Brazil |
France |
Germany |
Hong Kong |
Italy |
Korea, Republic of |
Russian Federation |
Singapore |
Spain |
Taiwan |
Thailand |
Turkey |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Phase Ib will end when all patients have discontinued treatment or at least 1 year after the last patient was included in phase Ib of the study.
Phase II of the study will end when all patients have discontinued treatment or at least 1 year after the last patient was included in phase II of the study.
The study will be considered as closed when the phase Ib as well as the phase II parts have ended. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |