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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03522064




Registration number
NCT03522064
Ethics application status
Date submitted
17/04/2018
Date registered
11/05/2018
Date last updated
18/09/2019

Titles & IDs
Public title
Bipolar Androgen Therapy in Metastatic Castrate Resistant Prostate Cancer With Homologous Recombination Deficiency
Scientific title
High Dose Testosterone in Men With Advanced Prostate Cancer and Homologous Recombination Deficiency
Secondary ID [1] 0 0
HiTECH
Universal Trial Number (UTN)
Trial acronym
HiTeCH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Castration-resistant Prostate Cancer 0 0
Homologous Recombination Deficiency 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Testosterone Enanthate

Experimental: High dose testosterone - 500mg IM enanthate every 4 weeks in combination with ongoing LHRH agent (unless post-orchidectomy).


Treatment: Drugs: Testosterone Enanthate
Testosterone Enanthate is the oil-soluble ester of the androgenic hormone testosterone. Testosterone Enanthate is a clear to pale yellow solution for intramuscular injection. Each pre-filled syringe contains 250mg testosterone enanthate/1mL.

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

Outcomes
Primary outcome [1] 0 0
PSA Response Rate - >/= 50% fall from baseline PSA
Timepoint [1] 0 0
1 year
Secondary outcome [1] 0 0
Time to PSA progression - Time to increase in PSA >/=25% from baseline or nadir confirmed on subsequent test >1 week later
Timepoint [1] 0 0
1 year
Secondary outcome [2] 0 0
Quality of Life - FACT-P
Timepoint [2] 0 0
1 year
Secondary outcome [3] 0 0
Radiological Response Rate - RECIST or PCWG3 Criteria
Timepoint [3] 0 0
1 year
Secondary outcome [4] 0 0
Safety and Tolerability (Frequency of adverse events as assessed by NCI CTCAE v4.0) - Frequency of adverse events as assessed by NCI CTCAE v4.0
Timepoint [4] 0 0
1 year

Eligibility
Key inclusion criteria
1. Males with histologically confirmed adenocarcinoma of the prostate

2. Confirmed HRD (Homologous recombination defect) in germline and/or somatic DNA
analysis (tumour or blood), by a validated assay (see Appendix 1). Mutations in HR
genes not listed in appendix 1 will be considered in literature suggests
pathogenicity. A maximum of 10 uncharacterised or heterozygous mutations will be
included.

3. Age = 18 years

4. ECOG performance status = 1

5. Rising PSA confirmed on two sequential tests =1 week apart and a minimum value of 2
ug/L despite castrate levels of testosterone

6. Serum testosterone < 1.7 nmol/L and on an LHRH agent or post orchidectomy = 1 year.

7. Washout of = 4 weeks from prior line of treatment, radiotherapy or surgery (aside from
LHRH agent)

8. Adequate bone marrow function (platelets > 100 x 109/L, ANC > 1.5 x 109/L, Hb >100)

9. Adequate liver function (ALT/AST < 1.5 x ULN, bilirubin < 2 x ULN)

10. Adequate renal function (creatinine clearance > 50 ml/min)

11. Adequate cardiac function and reserve after cardiology assessment

12. Archived tissue sample available or willingness to undergo fresh biopsy

13. Willing and able to comply with all study requirements, including treatment, timing
and/or nature of required assessments

14. 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

2. Pain due to metastatic prostate cancer requiring opioid analgesics

3. Evidence of disease progression in sites or extent that, in the opinion of the
investigator, would put the patient at risk from testosterone therapy and its
potential for initial tumour flare (eg: femoral metastasis at risk of fracture,
ureteric obstruction due to nodal disease or cord compression due to spinal
metastases).

4. Previous treatment with platinum chemotherapy and/or a PARP inhibitor. However up to 8
men with prior treatment to these agents will be included as an exploratory cohort.

5. Life expectancy of less than 3 months.

6. Brain metastases or leptomeningeal disease

7. History of thromboembolic event and not currently on anticoagulation

8. Prior myocardial infarction or unstable angina within 2 years of study entry

9. Haematocrit = 50%, untreated severe obstructive sleep apnoea or poorly controlled
heart failure (NYHA >1)

10. History of another malignancy within 5 years prior to registration. Patients with a
past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the
skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma
of the bladder are eligible. Patients with a history of other malignancies are
eligible if they have been continuously disease free for at least 5 years after
definitive primary treatment.

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

12. Presence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule,
including alcohol dependence or drug abuse.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Single group
Other design features
Phase
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
Kinghorn Cancer Centre, St. Vincent's Hospital - Sydney
Recruitment postcode(s) [1] 0 0
2010 - Sydney

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine the efficacy of BAT in men with metastatic
castrate-resistant prostate cancer (mCRPC) and homologous recombination deficiency (HRD).
Bipolar androgen therapy will be administered to men confirmed to have HRD on tumour tissue
and/or circulating tumour DNA analysis on pre-screening.
Trial website
https://clinicaltrials.gov/show/NCT03522064
Trial related presentations / publications
Teply BA, Wang H, Luber B, Sullivan R, Rifkind I, Bruns A, Spitz A, DeCarli M, Sinibaldi V, Pratz CF, Lu C, Silberstein JL, Luo J, Schweizer MT, Drake CG, Carducci MA, Paller CJ, Antonarakis ES, Eisenberger MA, Denmeade SR. Bipolar androgen therapy in men with metastatic castration-resistant prostate cancer after progression on enzalutamide: an open-label, phase 2, multicohort study. Lancet Oncol. 2018 Jan;19(1):76-86. doi: 10.1016/S1470-2045(17)30906-3. Epub 2017 Dec 14.
Schweizer MT, Wang H, Luber B, Nadal R, Spitz A, Rosen DM, Cao H, Antonarakis ES, Eisenberger MA, Carducci MA, Paller C, Denmeade SR. Bipolar Androgen Therapy for Men With Androgen Ablation Naïve Prostate Cancer: Results From the Phase II BATMAN Study. Prostate. 2016 Sep;76(13):1218-26. doi: 10.1002/pros.23209. Epub 2016 Jun 24.
Public notes

Contacts
Principal investigator
Name 0 0
Anthony M Joshua, MBBS, PhD, FRACP
Address 0 0
St. Vincent's Hospital-Manhattan
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/NCT03522064