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

Recruitment & Eligibility

Status: Recruiting

Sex: Male

Target Recruitment: Not specified

Inclusion 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.