None listed
Conditions
Brief summary
This study will evaluate the effects of a drug, AUY922 which inhibits heat shock protein 90 and may disrupt cancer cell growth in men with high-risk, localised protate cancer. You may be eligible to join this study if you are male, aged 18 years or over and have been diagnosed with prostate cancer and scheduled for a prostectomy surgery. The majority of men diagnosed with prostate cancer have disease confined to their prostate and surgery and/or radiotherapy offers a potential cure. However many men can have the cancer return within 5 - 7 years. Treatments for these men with recurrent prostate cancer are limited. The purpose of this study is to answer the question if treatment with a new drug called AUY922 (a 60 minute intravenous infusion at 70 mg/m2 on days 1, 8, 15 and 22 over a 28 day cycle) can stop the growth of prostate cancer cells. Prostate cancer cell growth can be measured by a protein called Ki67. Prostate tissue from biopsies from men with prostate cancer will be collected before treatment with AUY922. All men approached will be having a prostatectomy. After patients have received treatment, their prostate tissue will be collected at surgery evaluated for expression of Ki67. It is hypothesised that Ki67 expression will be 50% lower compared with before treatment. If there is sufficient activity in the first 25 men who receive treatment, the study will continue to a full experimental cohort of 41 patients. Fourteen (14) patients will be recruited to be a control group with no treatment prior to prostatectomy.
Interventions
AUY922 administered via a 60 minute intravenous infusion at 70 mg/m2 on days 1, 8, 15 and 22 over a 28 day cycle
Sponsors
The University of Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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)
Exclusion criteria
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.
Outcome results
None listed