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Bipolar Androgen Therapy + Carboplatin in mCRPC

PHASE2RECRUITING

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

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

Males with histologically confirmed adenocarcinoma of the prostate

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.

Age ≥ 18 years

ECOG performance status ≤ 1

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

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

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

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

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

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

Adequate cardiac function and reserve after cardiology assessment

Archived tissue sample available or willingness to undergo fresh biopsy

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

Signed, written informed consent

Exclusion criteria

Contraindications to investigational product

Pain due to metastatic prostate cancer requiring opioid analgesics

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).

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.

Life expectancy of less than 3 months.

Brain metastases or leptomeningeal disease

History of thromboembolic event and not currently on anticoagulation

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

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

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.

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

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.

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: Male

Things to know

Study dates

Study start: 2018-07-30

Primary completion: 2024-12-30

Study completion finish: 2025-12-30

Study type

TREATMENT

Phase

PHASE2

Trial ID

NCT03522064

Intervention or treatment

DRUG: Testosterone Enanthate 100 MG/ML Injectable Solution

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

Conditions

• Castration-resistant Prostate Cancer
• Homologous Recombination Deficiency

Image related to Castration-resistant Prostate Cancer

Condition: Castration-resistant Prostate Cancer, Homologous Recombination Deficiency
DRUG: Testosterone Enanthate 100 MG/ML Injectable Solution and other drugs
Sydney, New South Wales, Australia
Sponsor: St Vincent's Hospital, Sydney

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Kinghorn Cancer Centre, St. Vincent's Hospital

Research sites nearby

Select from list below to view details:

Kinghorn Cancer Centre, St. Vincent's Hospital
Sydney, New South Wales, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: High dose testosterone + Carbolplatin 500mg IM enanthate every 4 weeks in combination with ongoing LHRH agent (unless post-orchidectomy) plus Carboplatin AUC 5	DRUG: 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.

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
PSA Response Rate	\>/= 50% fall from baseline PSA	1 year

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Time to PSA progression	Time to increase in PSA \>/=25% from baseline or nadir confirmed on subsequent test \>1 week later	1 year
Radiological Response Rate	RECIST or PCWG3 Criteria	1 year
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	1 year

Frequently Asked Questions

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References

Clinical Trials Gov: Bipolar Androgen Therapy + Carboplatin in mCRPC