High-dose Testosterone in Men With Metastatic Castration-resistant Prostate Cancer and ATM or CDK12 Deficiency
This study will determine whether the presence of DNA repair deficiency in the form of alterations in the genes ATM, CDK12 or CHEK2 predicts for a high likelihood of responding to the use of intermittent high dose testosterone. This therapy may result in responses in tumors which are genetically unstable because of DNA repair deficiency and this is a prospective study to test that hypothesis
• 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.