Bipolar Androgen Therapy + Carboplatin in mCRPC (HiTeCH)

  • STATUS
    Recruiting
  • End date
    Dec 30, 2022
  • participants needed
    30
  • sponsor
    St Vincent's Hospital, Sydney
Updated on 12 February 2022
gonadotropin
androgens
testosterone
orchiectomy
serum testosterone
adenocarcinoma
androgen therapy
adenocarcinoma of prostate

Summary

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

Description

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

Details
Condition Castration-resistant Prostate Cancer, Homologous Recombination Deficiency
Treatment testosterone enanthate, Testosterone Enanthate 100 MG/ML Injectable Solution, Testosterone Enanthate 100 MG/ML Injectable Solution / Carboplatin AUC 5
Clinical Study IdentifierNCT03522064
SponsorSt Vincent's Hospital, Sydney
Last Modified on12 February 2022

Eligibility

Yes No Not Sure

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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