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Trial registered on ANZCTR


Registration number
ACTRN12614000789662
Ethics application status
Approved
Date submitted
16/06/2014
Date registered
24/07/2014
Date last updated
13/01/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating a new drug (AUY922) for controlling prostate cancer cell growth using laboratory based outcomes in men with high risk prostate cancer
Scientific title
A Randomised controlled Phase II trial of the pharmacodynamic effects of the heat shock protein 90 (Hsp90) inhibitor AUY922 in high-risk, localised prostate cancer
Secondary ID [1] 284807 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 292185 0
Condition category
Condition code
Cancer 292525 292525 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
AUY922 administered via a 60 minute intravenous infusion at 70 mg/m2 on days 1, 8, 15 and 22 over a 28 day cycle
Intervention code [1] 289597 0
Treatment: Drugs
Comparator / control treatment
Best standard care - no study drug administered prior to prostatectomy surgery
Control group
Active

Outcomes
Primary outcome [1] 292385 0
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)
Timepoint [1] 292385 0
After four weeks of treatment or at radical prostatectomy
Secondary outcome [1] 308844 0
Hsp90 inhibition demonstrated by immunohistochemistry and ELISA induction of Hsp 70
Timepoint [1] 308844 0
After four weeks of treatment or radical prostectomy
Secondary outcome [2] 308845 0
Apoptotic cell death by increase in caspase-3 immunohistochemistry
Timepoint [2] 308845 0
After four weeks of treatment or radical prostectomy
Secondary outcome [3] 308846 0
Changes in serum or tumour levels of PSA
Timepoint [3] 308846 0
After four weeks of treatment or radical prostectomy
Secondary outcome [4] 308847 0
Pathological regression defined by cancer cell atrophy
Timepoint [4] 308847 0
After four weeks of treatment or radical prostectomy
Secondary outcome [5] 308848 0
Incidence of adverse events as reported by either the treating oncologist or surgeon. Examples of adverse events include fatigue, diarrhoea or nausea.
Timepoint [5] 308848 0
During treatment and 30 days after last dose

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
3:1 randomisation in favour of treatment
Phase
Phase 2
Type of endpoint/s
Pharmacodynamics
Statistical methods / analysis
A two-stage minimax design will be used to test the primary hypothesis about the frequency of pharmacodynamic (PD) responses in treated patients, with a response defined as 50% or greater decrease in Ki-67 expression in the paired prostate biopsy baseline sample compared with the radical prostatectomy sample.

If fewer than 3 responses are observed in the first 25 treated patients then consideration will be given to modifying or stopping the study. The regimen will be considered to have sufficient activity (greater than or equal to 30% response rate) if at the end of the study at least 8 patients among the 41 treated patients achieve a response.
Fourteen untreated men will be enrolled in the control group to provide estimates of PD biomarkers as a basis for comparison giving a total sample size of 55 patients.


Analysis of efficacy endpoints (i.e., response, biomarkers) will include only evaluable patients. Analysis of safety endpoints (i.e., toxicity) will be according to treatment received, including only patients who received at least 1 dose of the experimental treatment. Where appropriate p-values will be two tailed. A nominal significance level of 0.05 will be applied. Analysis will be performed when evaluable tissue is available from 25 participants treated with AUY922 and at study completion.
Adverse events will be assessed at the interim analysis and at the completion of the study. Serious adverse events will be monitored by the trial management committee on an ongoing basis to ensure that the rate of these events remains acceptable for the study.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2016
Actual
Date of last participant enrolment
Anticipated
19/09/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
55
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 2637 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment postcode(s) [1] 8294 0
2050 - Missenden Road

Funding & Sponsors
Funding source category [1] 289421 0
Government body
Name [1] 289421 0
Cancer Australia
Country [1] 289421 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney
NSW 2006
Australia
Country
Australia
Secondary sponsor category [1] 288104 0
None
Name [1] 288104 0
Nil
Address [1] 288104 0
Country [1] 288104 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291179 0
SLHD Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 291179 0
Ethics committee country [1] 291179 0
Australia
Date submitted for ethics approval [1] 291179 0
12/05/2014
Approval date [1] 291179 0
22/07/2014
Ethics approval number [1] 291179 0
EC00113

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49214 0
A/Prof Lisa Horvath
Address 49214 0
Chris O'Brien Lifehouse
119-143 Missenden Road
Camperdown NSW 2050
Country 49214 0
Australia
Phone 49214 0
+61285140149
Fax 49214 0
Email 49214 0
hsp90@ctc.usyd.edu.au
Contact person for public queries
Name 49215 0
Hsp90 inhibitor study coordinator
Address 49215 0
NHMRC Clinical Trials Centre
Chris O'Brien Lifehouse
119-143 Missenden Road
Camperdown NSW 2050
Country 49215 0
Australia
Phone 49215 0
+61295625000
Fax 49215 0
Email 49215 0
hsp90@ctc.usyd.edu.au
Contact person for scientific queries
Name 49216 0
Lisa Horvath
Address 49216 0
Chris O'Brien Lifehouse
119-143 Missenden Road
Camperdown NSW 2050
Country 49216 0
Australia
Phone 49216 0
+61285140149
Fax 49216 0
Email 49216 0
hsp90@ctc.usyd.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.