E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
female patients with HER2-positive, locally advanced, recurrent or
metastatic breast cancer
after failure of Trastuzumab treatment who received at least 1 but no
more than 2 prior anti-
HER2-based regimens including at least 1 Trastuzumab containing
regimen. |
|
E.1.1.1 | Medical condition in easily understood language |
women with advanced HER2-positive breast cancer, that has progressed
on or after prior Herceptin treatment |
|
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 | 14.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
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 1b: Define the maximum tolerated dose (MTD) and/or the
recommended phase two dose (RPTD) of AUY922 in combination with
Trastuzumab
Phase II: Evaluate preliminary anti-tumor activity of AUY922 in
combination with Trastuzumab in adult patients with advanced or
metastatic HER2- positive breast cancers. |
|
E.2.2 | Secondary objectives of the trial |
Phase Ib:
- Characterize the safety and tolerability of AUY922 when administered
in combination with Trastuzumab
Phase II:
- Characterize the safety and tolerability of the combination with
Trastuzumab at the RPTD
- Assess the efficacy at the RPTD (Progression Free Survival, Overall
Survival)
Phase Ib and II:
- Characterize the pharmacokinetic profile of AUY922 and its metabolite
BJP762, when given in combination with Trastuzumab |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Female pts with confirmed HER2-positive, non-operable locally advanced or metastatic breast cancer.
• All patients must have at least one measurable lesion as defined by
RECIST criteria.
• All patients must have documented progressive disease following the
last line of therapy before entering the study
• ECOG Performance status ≤ 1
Other protocol-defined inclusion criteria apply. |
|
E.4 | Principal exclusion criteria |
• Patients with known CNS metastasis which are symptomatic or require treatment for symptom control and/or growing.
• Prior treatment with any HSP90 or HDAC inhibitor.
• Impaired cardiac function
• Acute or chronic liver or renal disease
• Patients who are currently receiving treatment with any medication
which has a relative risk of prolonging the QTc interval or inducing
Torsades de Pointes and cannot be switched or discontinued to an
alternative drug prior to commencing AUY922
• Patients with a history of another primary malignancy that is currently
clinically significant or currently requires active intervention
• Patients who do not have either an archival tumor sample available or
are unwilling to have a fresh tumor sample collected at baseline.
Other protocol-defined exclusion criteria apply |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint of phase Ib:
- Incidence rate of Dose-Limiting Toxicities (DLT)
Primary endpoint of phase II:
- Overall response rate (ORR) as assessed by RECIST |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase Ib: throughout the first cycle
Phase II: at the protocol-defined timepoints |
|
E.5.2 | Secondary end point(s) |
Phase Ib and II:
- Safety: Adverse drug reactions and serious adverse drug reactions,
changes in hematology and chemistry values, specifically those
associated with hepatic and renal function; assessment of physical
examinations, neurological exams, vital signs and electrocardiograms.
- Pharmacokinetics: Exposure of AUY922 in plasma. PK parameters such
as AUC, Cmax, Ctrough and t1/2.
Phase II:
- Efficacy: Progression-free survival (PFS) and Overall Survival (OS) as
defined in RECIST guidelines |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
throughout the study (safety) and at protocol-defined timepoints
(efficacy, PK) |
|
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 | No |
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 |
MTD / recommended phase 2 dose of combination AUY922 / Herceptin |
|
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
France |
Germany |
Italy |
Netherlands |
Singapore |
Spain |
Sweden |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |