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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03513211




Registration number
NCT03513211
Ethics application status
Date submitted
17/04/2018
Date registered
1/05/2018
Date last updated
18/09/2019

Titles & IDs
Public title
Phase I/II Study of Hydroxychloroquine With Itraconazole With Biochemically Recurrent Prostate Cancer
Scientific title
A Phase I/II Study of Hydroxychloroquine and Itraconazole as Therapy for Men With Androgen Normalised Prostate Cancer
Secondary ID [1] 0 0
HITMAN
Universal Trial Number (UTN)
Trial acronym
HITMAN-PC
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SUBA-itraconazole
Treatment: Drugs - Hydroxychloroquine

Experimental: Dose escalation arm - Suba-itraconazole in combination dose escalating hydroxychloroquine H

Experimental: Phase II: Dose expansion arm - Suba-itraconazole with recommended phase II dose of hydroxychloroquine as determined by phase I arm.


Treatment: Drugs: SUBA-itraconazole
150mg PO BD

Treatment: Drugs: Hydroxychloroquine
Escalating doses in Rolling 6 Phase I

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Determination of Recommended Phase II Dose of Hydroxychloroquine in combination with Suba-itraconazole - Recommended Phase II Dose
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
PSA response rate - Fall in PSA >/=50% from baseline
Timepoint [1] 0 0
1 year
Secondary outcome [2] 0 0
Composite safety - Rate of adverse events defined by CTCAE criteria
Timepoint [2] 0 0
1 year
Secondary outcome [3] 0 0
Time to ADT commencement - Time to start of ADT
Timepoint [3] 0 0
1 year
Secondary outcome [4] 0 0
Metastasis-free survival - Time from commencement of treatment to first metastatic lesion on CT or WBBS
Timepoint [4] 0 0
1 year

Eligibility
Key inclusion criteria
1. Males = 18 years of age with histologically or cytologically confirmed adenocarcinoma
of the prostate without neuroendocrine differentiation or small cell features

2. Prostate cancer initially treated by radical prostatectomy, radiotherapy (including
brachytherapy) or both, with curative intent

3. PSA = 1 ng/ml with at least two sequential rises at least 1 week apart according to
PCWG3.

4. Serum testosterone = 5 nmol/L

5. QTc = 470 msec using Fridericia correction formula

6. Adequate bone marrow function with platelets = 100 x 10^9/L, ANC = 1.5 x 10^9/L, Hb =
100 g/L in the absence of transfusion

7. Adequate liver function with ALT/AST < 1.5 x ULN, bilirubin < 1.5 x ULN

8. Adequate renal function with creatinine clearance > 50 ml/min

9. ECOG Performance Status = 1

10. Able to start study treatment within 28 days of consent

11. Willing and able to comply with all study requirements, including treatment (e.g. able
to swallow tablets), timing and/or nature of required assessments

12. Signed, written informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Contraindications to investigational product including hypersensitivity, treatment
with any CYP3A4 inducer or inhibitor or known G6PD deficiency. If on a statin, must be
changed to rosuvastatin or ceased, as appropriate

2. Evidence of metastatic disease on conventional WBBS or CT. However low volume regional
nodes (= N1, up to the aortic bifurcation) may be accepted in asymptomatic patients.

3. PSA doubling time = 3 months calculated using MSKCC calculator
(https://www.mskcc.org/nomograms//prostate/psa-doubling-time)

4. Prior systemic therapy for advanced cancer prostate cancer such as hormonal therapy or
chemotherapy; neo/adjuvant hormonal therapy allowed if = 24 months total duration and
ceased = 12 months prior to enrolment

5. Life expectancy of = 1 year

6. History of another invasive cancer within 3 years before screening with the exception
of fully treated cancer with remote probability of recurrence

7. Concurrent illness, including severe infection that may jeopardize the ability of the
patient to undergo the procedures outlined in this protocol with reasonable safety

8. Use of hydroxychloroquine and/or itraconazole for any indication in the preceding 2
years or at any time for treatment of prostate cancer.

8. Serious medical or psychiatric conditions that might limit the ability of the patient to
comply with the protocol.

9. Men must have been surgically sterilised or use a barrier method of contraception.

10. Pre-existing retinopathy, keratopathy or other ocular pathologies that, in the opinion
of an ophthalmologist would put the patient at risk of hydroxychloroquine induced
retinopathy 11. History of cardiac failure or recent history if ischaemic heart disease (<2
years)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St Vincent's Hospital - Darlinghurst
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst

Funding & Sponsors
Primary sponsor type
Other
Name
St Vincent's Hospital, Sydney
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Recent pre-clinical work has suggested that Itraconazole has an anti-cancer effect that works
synergistically with hydroxychloroquine. This may delay the need for androgen deprivation
therapy (ADT) and its associated toxicities in men with biochemically recurrent (BCR)
prostate cancer. This study aims to determine feasibility, safety and efficacy of
suba-itraconazole (SI) in combination with hydroxychloroquine (HQ) in the treatment of
biochemically recurrent (BCR) prostate cancer as means of delaying time to commencement of
androgen deprivation therapy.
Trial website
https://clinicaltrials.gov/show/NCT03513211
Trial related presentations / publications
Suzman DL, Antonarakis ES. High-dose itraconazole as a noncastrating therapy for a patient with biochemically recurrent prostate cancer. Clin Genitourin Cancer. 2014 Apr;12(2):e51-3. doi: 10.1016/j.clgc.2013.11.015. Epub 2013 Nov 14.
Farrow JM, Yang JC, Evans CP. Autophagy as a modulator and target in prostate cancer. Nat Rev Urol. 2014 Sep;11(9):508-16. doi: 10.1038/nrurol.2014.196. Epub 2014 Aug 19. Review.
Public notes

Contacts
Principal investigator
Name 0 0
Anthony Joshua, MBBS(Hons) PhD
Address 0 0
St Vincent's Hospital, Sydney
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Robert Kent
Address 0 0
Country 0 0
Phone 0 0
+61293555611
Fax 0 0
Email 0 0
SVHS.CancerResearch@svha.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03513211