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

About This Trial

This study is testing whether giving high doses of testosterone in cycles can help shrink or control advanced prostate cancer.
It is designed specifically for patients whose cancer has spread, stopped responding to standard hormone therapies, and carries specific gene changes—known as ATM, CDK12, or CHEK2—that affect how cancer cells repair themselves.
To take part, you must have already tried a newer hormone-blocking medication and currently have little to no cancer-related pain.
Before considering this trial, you should know that it is not suitable for people whose cancer has spread to the liver or brain, or for those who need strong prescription opioid medications to manage pain.

More Information

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

Who Can Enroll

Age Range: 18 years and older
Gender: Male
Who This Trial is For: This study is testing whether giving high doses of testosterone in cycles can help shrink or control advanced prostate cancer.

Study Details

Start Date: August 31, 2021
Lead Sponsor: VA Office of Research and Development

Full 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
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 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 2.5 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