A phase I dose escalation, multi-center, open-label study of AUY922 administered IV on a once-weekly schedule in adult patients with advanced solid malignancies including phase II expansion arms in patients with either HER2 positive or ER positive locally advanced or metastatic breast cancer.
- Conditions
- Solid tumors and metastatic breastcancer10006291
- Registration Number
- NL-OMON32784
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 11
Breast cancer phase II expansion arms only
1a. Female patients with ER positive HER2 positive locally advanced non-operable metastatic breast cancer with history of trastuzumab resistance
1b. Female patients with ER positive non-operable locally advanced or metastatic breast
cancer who received endocrine therapy and whose disease has
progressed on at least one line of endocrine therapy for advanced disease.
2. At least one measurable lesion as defined by RECIST.
3. All patients must have progressive disease before entering to the study.
4. (WHO) Performance Status of * 2.
5. Life expectancy of * 12 weeks.
6. Patients must have the following laboratory values:
* Absolute Neutrophil Count (ANC) * 1.5 x 109/L
* Hemoglobin (Hgb) * 9 g/dl
* Platelets (plt) * 100 x 109/L
* Potassium, calcium, magnesium and phosphorus within normal limits or correctable with supplements
* Liverfunctiontests * 2.5 x Upper Limit of Normal (ULN) or * 5.0 x ULN if liver metastases are present
* bilirubin and creatinin * 1.5 x ULN or 24-hour clearance * 50 ml/min
* albumin * 2.5g/dl
Main Exclusion criteria
1. CNS metastasis.
2. Prior treatment with any HSP90 or HDAC inhibitor compound.
3a. Radiotherapy within 4 weeks or palliative radiotherapy within 2 weeks
3b. Nitrosoureas, mitomycin and monoclonal antibodies, such as trastuzumab: within 6 weeks
3c. Systemic anticancer treatment for which the recovery period
is not known, or investigational drugs within a duration of * 5 half lives of the agent and their active metabolites (if any)
4. Patients who have not recovered from side effects of previous systemic anticancer therapy to less than grade 2 prior to the first dose of study treatment
5. Treatment with therapeutic doses of sodium warfarin (Coumadin). Low doses of
Coumadin (e.g. * 2mg/day for line patency) are permitted.
6. Patients using medications that are substrates, inhibitors or inducers of CYP3A4,
CYP2C8, CYP2C9 and CYP2C19 and cannot be switched or discontinued to an
alternative drug prior to commencing AUY922 dosing
7. Unresolved diarrhea * CTCAE grade 2.
8. Patients who do not have either an archival tumor sample available or are unwilling to have a fresh tumor sample collected at baseline.
9. Acute or chronic liver disease.
10. Acute or chronic renal disease.
11. Other concurrent severe and/or uncontrolled medical conditions
12. Clinical significant cardiac disease e.g:
* History of long QT syndrome or Mean QTc * 450 msec
* History of clinically manifest ischemic heart disease * 6 months prior to
study start.
* History of heart failure or left ventricular (LV) dysfunction (LVEF * 45%) by MUGA
or ECHO.
* Clinically significant ECG abnormalities
* History of atrial fibrillation, atrial flutter or ventricular arrhythmias
* Clinically significant resting bradycardia (< 50 beats per minute).
* Any medication which has a relative risk or prolonging the QTcF interval or inducing Torsades de Pointes
* Pacemaker.
13. Patients with known disorders due to a deficiency in bilirubin glucuronidation
14. Patients with a history of 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 I: to determine the MTD of AUY922 as a single agent, administered once<br /><br>weekly. Estimation of the MTD will be based upon the estimation of the<br /><br>probability of DLT in cycle 1.<br /><br><br /><br>Phase II only (breast cancer)<br /><br>Efficacy: responders (CR/PR), non-responders with stable disease for at least 6<br /><br>months (SD * 6 months), progressive disease within 6 months from study start or<br /><br>others </p><br>
- Secondary Outcome Measures
Name Time Method <p>* Safety: Type, frequency and severity of adverse events (CTCAE Version 3.0)<br /><br>* Efficacy: In the dose-escalation arm response will be also assessed by RECIST.<br /><br>* PK: Cmax, Tmax, AUC0-24 and AUC0-T<br /><br>* PD: PET response, blood and tumor biomarkers at baseline and post-AUY922<br /><br>dosing.</p><br>