A phase Ib/II, multi-center, open-label study to evaluate the efficacy of AUY922 in combination with Trastuzumab in patients with locally advanced or metastatic HER2-positive breast cancer, that has progressed after or during at least one Trastuzumab-containing regimen.
- Conditions
- advanced HER-2 positiv breastcancer10006291
- Registration Number
- NL-OMON36445
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 3
- Confirmed HER2-positive, non-operable locally advanced or metastatic breast cancer
- Tumor samples must demonstrate HER2 over-expression based on either:
- Immunohistochemistry (IHC) 3+ or IHC 2+ confirmed by fluorescence in-situ hybridization (FISH).
- At least 1 but no more than 2 prior anti-HER2 based regimens including at least 1 regimen containing Trastuzumab.
- At least one measurable lesion as defined by RECIST.
-ECOG Performance Status of <= 1
• Patients must have the following laboratory values:
Absolute Neutrophil Count >=1.5x109/L
Hemoglobin >= 9 g/dl = 5.58 mmol/l
Platelets >=100x109/L
Potassium, total calcium and phosphorus within normal limits
Magnesium above LLN
Adequate liver function defined as:
AST/SGOT and ALT/SGPT <= 1.5 x Upper Limit of Normal or
AST/SGOT and ALT/SGPT <= 2.5 x Upper Limit of Normal (ULN) if <= 5.0 x ULN if liver metastases are present
Serum bilirubin <= 1.5 x ULN
Serum albumin > 2.5 g/dl
Serum creatinine <= 1.5 x ULN or 24-hour clearance >= 50 ml/min.
• Negative serum pregnancy test.
• 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.
• Systemic anti-cancer treatment prior to the first dose of AUY922 within the following time frames:
- Palliative radiotherapy: within 2 weeks
- Nitrosoureas, mitomycin: within 6 weeks
• Unresolved diarrhea >= CTCAE grade 1
• Reversible side effects of previous systemic anticancer therapy (except for alopecia) to less than CTCAE grade 2 prior to the first dose.
• Therapeutic doses of sodium warfarin (Coumadin).
• Acute or chronic liver or renal disease.
• Patients with other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol.
• Known hypersensitivity to any study medication.
• Impaired cardiac function, including any one of the following:
- History (or family history) of long QT syndrome.
- Mean QTcF >= 450 msec on screening ECG.
- History of clinically manifested ischemic heart disease <= 6 months prior to study start.
- (LVEF <= 45%) by MUGA or ECHO.
- Clinically significant ECG abnormalities
- History or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes.
- Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
- Clinically significant resting bradycardia (< 50 beats per minute).
- Current treatment with any medication which has a relative risk of prolonging the QTcF interval or inducing Torsades de Pointes
- Obligate use of a cardiac pacemaker.
• Another primary malignancy that is currently clinically significant or currently requires active intervention.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Phase Ib:<br /><br>- Incidence rate of Dose Limiting Toxicities (DLT)<br /><br>Phase II:<br /><br>- Overall response rate (ORR)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Phase Ib and II<br /><br>- Safety: Adverse drug reactions , changes in hematology and chemistry values,<br /><br>specifically those associated with hepatic and renal function; assessment of<br /><br>physical examinations, neurological exams, vital signs and electrocardiograms.<br /><br>- Pharmacokinetics: Cmax, Tmax, AUC0-tlast and AUC(0-infinity)<br /><br><br /><br>Phase Ib:<br /><br>- Preliminary efficacy: Tumor response assessment using CT/MRI.<br /><br>- Pre vs. serial post-treatment intracellular protein measurement of HSP70 in<br /><br>PBMCs<br /><br><br /><br>Phase II:<br /><br>- -PFS/OS as defined in RECIST guidelines.<br /><br>-Temporal and magnitude changes in blood and tissue marker levels comparing<br /><br>pre- vs. post-treatment.</p><br>