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

Eligibility Criteria

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.