RecruitingPhase 2NCT03522064

Bipolar Androgen Therapy + Carboplatin in mCRPC

High Dose Testosterone + Carboplatin in Men With Advanced Prostate Cancer

Sponsor

St Vincent's Hospital, Sydney

Enrollment

30 participants

Start Date

Jul 30, 2018

Study Type

INTERVENTIONAL

Conditions

Homologous Recombination Deficiency Castration-resistant Prostate Cancer

Summary

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

Eligibility

Sex: MALEMin Age: 18 Years

Inclusion Criteria14

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 Criteria12

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.

Interventions

DRUGTestosterone 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.

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