Bipolar Androgen Therapy + Carboplatin in mCRPC

NCT ID: NCT03522064

Last Updated: 2025-05-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-30

Study Completion Date

2025-12-30

Brief Summary

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The purpose of this study is to determine the efficacy of BAT and carboplatin in men with metastatic castrate-resistant prostate cancer (mCRPC).

Detailed Description

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Androgen deprivation therapy (ADT) remains the mainstay of prostate cancer treatment. Though an effective therapy initially, the side effects of ADT are numerous and treatment resistance is inevitable. Castrate-refractory prostate cancer (CRPC) progresses via adaptive mechanisms that allow ongoing androgen receptor (AR) signalling despite castrate levels of androgens.

The concept of cycling between supra- and sub physiological levels of testosterone has been tested recently in studies of "bipolar androgen therapy" (BAT) in which patients are given high dose testosterone in combination with androgen deprivation therapy (ADT) via an LHRH agonist/antagonist. Studies of BAT using IM testosterone have been promising both in terms of PSA responses and quality of life improvements. Additionally, these early phase studies suggest the potential for re-sensitisation to novel anti-androgen therapies.

Though responses have been positive in these early studies a proportion of men fail to respond and data to guide patient selection is lacking. There are data to suggest that patients with DNA repair deficits may be particularly responsive to BAT. Whether these changes serve as predictors of response is unknown as the effect of BAT on the tumour, its microenvironment and peripheral circulating tumour DNA has not been studied in detail. Information on treatment effects may be key to appropriate patient selection for this treatment.

The aim of this study is to assess based on the pre-clinical studies, the combination with carboplatin

Conditions

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Castration-resistant Prostate Cancer Homologous Recombination Deficiency

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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High dose testosterone + Carbolplatin

500mg IM enanthate every 4 weeks in combination with ongoing LHRH agent (unless post-orchidectomy) plus Carboplatin AUC 5

Group Type EXPERIMENTAL

Testosterone Enanthate 100 MG/ML Injectable Solution

Intervention Type DRUG

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.

Testosterone Enanthate 100 MG/ML Injectable Solution / Carboplatin AUC 5

Intervention Type DRUG

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. Carboplatin as per standard procedures

Interventions

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Testosterone Enanthate 100 MG/ML Injectable Solution

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 Type DRUG

Testosterone Enanthate 100 MG/ML Injectable Solution / Carboplatin AUC 5

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. Carboplatin as per standard procedures

Intervention Type DRUG

Other Intervention Names

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Primoteston Depot

Eligibility Criteria

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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

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.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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St Vincent's Hospital, Sydney

OTHER

Sponsor Role lead

Responsible Party

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Anthony Joshua, FRACP

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Anthony M Joshua, MBBS, PhD, FRACP

Role: PRINCIPAL_INVESTIGATOR

St Vincent's Hospital

Locations

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Kinghorn Cancer Centre, St. Vincent's Hospital

Sydney, New South Wales, Australia

Site Status RECRUITING

Countries

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Australia

Central Contacts

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Robert Kent

Role: CONTACT

+61293555611

Facility Contacts

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Robert Kent

Role: primary

0293555611

References

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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.

Reference Type BACKGROUND
PMID: 29248236 (View on PubMed)

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 Naive 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.

Reference Type BACKGROUND
PMID: 27338150 (View on PubMed)

Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.

Reference Type DERIVED
PMID: 32203306 (View on PubMed)

Other Identifiers

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HiTECH

Identifier Type: -

Identifier Source: org_study_id

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