Combining Bipolar Androgen Therapy with Carboplatin for Advanced Prostate Cancer

High Dose Testosterone + Carboplatin in Men With Advanced Prostate Cancer

This study is testing if combining a new hormone treatment with a chemotherapy drug can help men with advanced prostate cancer that hasn't responded to other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: St Vincent's Hospital, Sydney (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Sydney, New South Wales)
• Trial ID: NCT03522064 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of bipolar androgen therapy (BAT) combined with carboplatin in men suffering from metastatic castrate-resistant prostate cancer (mCRPC). The approach involves cycling testosterone levels to potentially resensitize tumors to treatment after initial androgen deprivation therapy (ADT) has failed. Participants will be selected based on the presence of homologous recombination deficiency (HRD) in their cancer, which may indicate a better response to BAT. The study aims to gather data on treatment effects to improve patient selection for this innovative therapy.

Who should consider this trial

Good fit: Ideal candidates are males aged 18 and older with confirmed adenocarcinoma of the prostate and homologous recombination defects.

Not a fit: Patients without homologous recombination deficiencies or those who have not responded to prior treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for men with advanced prostate cancer who have limited treatment choices.

How similar studies have performed: Previous studies on bipolar androgen therapy have shown promising results, suggesting potential efficacy in similar patient populations.

Eligibility criteria

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.

Where this trial is running

Sydney, New South Wales

• Kinghorn Cancer Centre, St. Vincent's Hospital — Sydney, New South Wales, Australia (Recruiting)

Study contacts

• Principal investigator: Anthony M Joshua, MBBS, PhD, FRACP — St Vincent's Hospital
• Study coordinator: Robert Kent

Conditions Castration-resistant Prostate Cancer; Homologous Recombination Deficiency; Castrate-resistant prostate cancer; bipolar androgen therapy; homologous recombination deficiency; BRCA