High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers

Inclusion Criteria:

Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information
Male age > 18 years
Histologically or cytologically confirmed adenocarcinoma of the prostate
Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy. Patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy

Castration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and one of the following:

PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart.
Evaluable disease progression by modified RECIST 1.1 (Response Evaluation Criteria in Solid Tumors)
Progression of metastatic bone disease on bone scan with > 2 new lesions
Presence of metastatic disease on bone or CT scan
Patients must have progressed on 1 next-generation AR-signaling inhibitor (e.g. abiraterone, enzalutamide, apalutamide, darolutamide, etc.).
Asymptomatic or minimal cancer related symptoms
Eastern Cooperative Oncology Group (ECOG) Performance Status of < 2
Presence of inactivating mutations in ATM, CDK12 or CHEK2 as determined by a CLIA level assay for DNA sequencing.

Exclusion Criteria:

Currently receiving active therapy for other neoplastic disorders will not be eligible.
Histologic evidence of small cell carcinoma (morphology alone - immunohistochemical evidence of neuroendrocrine differentiation without morphologic evidence is not exclusionary)
Known parenchymal brain metastasis
Liver metastases
Active or symptomatic viral hepatitis or chronic liver disease AST or ALT > 2.5 x ULN or total bilirubin > ULN (unless Gilbert's syndrome is the etiology of hyperbilirubinemia).
Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of <35 % at baseline
Patients with pain attributable to their prostate cancer and requiring the use of opioids.
Tumor causing urinary outlet obstruction that requires catheterization for voiding. Patients that require catheterization to void secondary to benign strictures or other non-cancer causes will be permitted to enroll.
Presence of dementia, psychiatric illness, and/or social situations limiting compliance with study requirements or understanding and/or giving of informed consent.
Any condition(s), medical or otherwise, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained.