Evaluating a new drug (AUY922) for controlling prostate cancer cell growth using laboratory based outcomes in men with high risk prostate cancer
- Conditions
- Prostate CancerCancer - Prostate
- Registration Number
- ACTRN12614000789662
- Lead Sponsor
- The University of Sydney
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- Male
- Target Recruitment
- 55
1.Males with localised prostate cancer and at least clinical stage T3a Or Gleason score of between 8 and 10 Or Preoperative PSA greater than or equal to 20 ng/ml AND planned for radical prostatectomy
2.Age greater than or equal to 18 yrs
3.ECOG performance 0-1
4.Histological confirmation of prostate cancer via a pre-treatment diagnostic transrectal ultrasound (TRUS) biopsy.
5.Adequate bone marrow function with platelets greater than or equal to 100 x 109/L, neutrophils greater than or equal to 1.5 x 109/L and haemoglobin greater than or equal to 90 g/L;
6.Adequate hepatic function with serum total bilirubin less than or equal to 1.5 x upper limit of normal range and ALT/SGPT and SGOT/AST less than or equal to 2.5x upper limit of normal range (or less than 5.0 times ULN with documented liver metastases), serum albumin greater than 25 g/L. alkaline phosphatase less than or equal to 5x upper limit of normal range, and INR less than or equal to 1.5
7.Adequate renal function (with calculated creatinine clearance greater than 50 ml/min based on the Cockcroft-Gault method, 24 hour urine or GFR scan) and serum creatinine greater than 1.5 x Upper Limit of Normal range (ULN);
8.Serum calcium, potassium and magnesium within normal range or corrected with supplements
9.Study treatment both planned and able to start within 7 days of randomisation.
10.Willing and able to comply with all study requirements, including treatment and biospecimen collection
11.Signed, written informed consent (main study and biospecimen banking)
1.Major surgery less than or equal to 2 weeks prior to enrolment or who have not recovered from side effects of such therapy. Transrectal ultrasound (TRUS) biopsy is not considered major surgery in this study.
2.Known hypersensitivity to the study drug or its excipients
3.Patients with known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert’s syndrome)
4.Diarrhoea greater than or equal to CTCAE grade 2
5.Impaired cardiac function, including any one of the following:
a.History (or family history) of long QT syndrome
b.Mean QTcF greater than or equal to 450 msec on baseline ECG
c.History of clinically manifested ischemic heart disease less than or equal to 6 months prior to study start
d.History of heart failure or left ventricular (LV) dysfunction (LVEF less than or equal to 50%) by MUGA
e.Clinically significant ECG abnormalities
f.History or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes
g.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)
h.Clinically significant resting bradycardia (less than 50 beats per minute)
i.Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval or inducing Torsades de Pointes and cannot be discontinued or switched to an alternative drug prior to commencing start of treatment.
j.Obligate use of a cardiac pacemaker
6.Patients who have received prior antineoplastic therapy for advanced disease.
7.Prior treatment with an Hsp90 inhibitor
8.Patients receiving chronic or high dose corticosteroids therapy (Inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are allowed)
9.Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated.
10.Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary objective is to determine the effect of AUY922 on tumour cell proliferation (frequency of a 50% reduction in the Ki-67 proliferation index from the pre-treatment prostate biopsy compared to that present in prostate cancer tissue from radical prostatectomy)[After four weeks of treatment or at radical prostatectomy]
- Secondary Outcome Measures
Name Time Method Hsp90 inhibition demonstrated by immunohistochemistry and ELISA induction of Hsp 70 [After four weeks of treatment or radical prostectomy];Apoptotic cell death by increase in caspase-3 immunohistochemistry [After four weeks of treatment or radical prostectomy];Changes in serum or tumour levels of PSA[After four weeks of treatment or radical prostectomy];Pathological regression defined by cancer cell atrophy[After four weeks of treatment or radical prostectomy];Incidence of adverse events as reported by either the treating oncologist or surgeon. Examples of adverse events include fatigue, diarrhoea or nausea. [During treatment and 30 days after last dose]