Recruiting

Phase 2

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

Sponsor:

VA Office of Research and Development

Code:

NCT05011383

Conditions

Metastatic Prostate Cancer

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

High dose testosterone

Study Details

Brief summary:

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

Conditions

Metastatic Prostate Cancer

Study ID

NCT05011383

Start date

Aug 31, 2021

Status verified date

Jul, 2026

Completion date

Aug 31, 2027

Anticipated

Primary completion date

Aug 31, 2026

Anticipated

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

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 < 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.

Study Design

Enrollment

51 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: ATM

Patients with castration resistant prostate cancer which contains ATM alterations are treated with high dose testosterone

experimental: CDK12

Patients with castration resistant prostate cancer which contains CDK12 alterations are treated with high dose testosterone

experimental: CHEK2

Patients with castration resistant prostate cancer which contains CHEK2 alterations are treated with high dose testosterone

Interventions

High dose testosterone

High dose testosterone is administered subcutaneously once monthly until progression or toxicity

Primary outcome measure

PSA response [ Time Frame: 12 weeks ]

Central Contacts and Locations

Central contacts

Robert B Montgomery, MD

(206) 277-6878 Robert.Montgomery@va.gov

Elahe Mostaghel, MD

(206) 762-1010 emostagh@fhcrc.org

Locations

Rocky Mountain Regional VA Medical Center, Aurora, CO

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Daniel Bowles, MD

720-723-6498 Daniel.Bowles@va.gov

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Recruiting

West Haven, Connecticut, United States, 06516-2770

Contacts

Herta Chao, MD

203-937-3421 Herta.Chao@va.gov

North Florida/South Georgia Veterans Health System, Gainesville, FL

Recruiting

Gainesville, Florida, United States, 32608

Contacts

Jess D Delaune, MD

352-988-7504 Jess.Delaune@va.gov

Orlando VA Medical Center, Orlando, FL

Recruiting

Orlando, Florida, United States, 32803

Contacts

Priya K Gopalan, MD

407-631-2389 Priya.Gopalan@va.gov

Atlanta VA Medical and Rehab Center, Decatur, GA

Recruiting

Decatur, Georgia, United States, 30033

Contacts

Maria Ribeiro, MD

404-728-7680 Maria.Ribeiro@va.gov

Robley Rex VA Medical Center, Louisville, KY

Recruiting

Louisville, Kentucky, United States, 40206-1433

Contacts

Fred Hendler, MD

502-287-3515

Kansas City VA Medical Center, Kansas City, MO

Recruiting

Kansas City, Missouri, United States, 64128

Contacts

Linda Verkruyse, MD

817-681-7115 Linda.Verkruyse@va.gov

St. Louis VA Medical Center John Cochran Division, St. Louis, MO

Recruiting

St Louis, Missouri, United States, 63106

Contacts

Eric Knoche, MD

314-289-6305 Eric.Knoche@va.gov

Durham VA Medical Center, Durham, NC

Recruiting

Durham, North Carolina, United States, 27705

Contacts

Rhonda Bitting, MD

919-286-0411 Rhonda.Bitting@va.gov

Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC

Recruiting

Salisbury, North Carolina, United States, 28144

Contacts

Michael Goodman, MD

704-638-9000

VA Portland Health Care System, Portland, OR

Recruiting

Portland, Oregon, United States, 97239

Contacts

Julie Graff, MD

503-220-8262 Julie.Graff@va.gov

Ralph H. Johnson VA Medical Center, Charleston, SC

Recruiting

Charleston, South Carolina, United States, 29401-5799

Contacts

Steven Savage, MD

843-792-4531 Stephen.Savage@va.gov

Memphis VA Medical Center, Memphis, TN

Recruiting

Memphis, Tennessee, United States, 38104-2127

Contacts

Alva Weir, MD

901-523-8990

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Recruiting

Nashville, Tennessee, United States, 37212-2637

Contacts

Sally York, MD

615-873-6979

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Recruiting

Seattle, Washington, United States, 98108-1532

Contacts

Robert B Montgomery, MD

(206) 277-6878 Robert.Montgomery@va.gov

Principal Investigator:

Robert B. Montgomery, MD

William S. Middleton Memorial Veterans Hospital, Madison, WI

Recruiting

Madison, Wisconsin, United States, 53705-2254

Contacts

David Kosoff, MD

608-256-1901 David.Kosoff@va.gov

More Information

Sponsor

VA Office of Research and Development

Last update posted

Jul 23, 2026

Last verified

Jul, 2026

Keywords

Prostatic Neoplasms

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-07-23.