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

NCT05011383 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: SPLP-003-20F
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 17

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

Keywords

Prostatic Neoplasms

Outcome Measures

Primary Outcomes (1)

• PSA response

  PSA response as measured by a 50% decline from baseline maintained for 12 weeks

  12 weeks

Study Arms (3)

ATM

EXPERIMENTAL

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

Drug: High dose testosterone

CDK12

EXPERIMENTAL

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

Drug: High dose testosterone

CHEK2

EXPERIMENTAL

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

Drug: High dose testosterone

Interventions

High dose testosterone DRUG

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

Also known as: Bipolar androgen therapy

ATM; CDK12; CHEK2

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Prostate cancer only develops in males
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Currently receiving active therapy for other neoplastic disorders will not be eligible.
• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (17)

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, 80045, United States

RECRUITING

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

West Haven, Connecticut, 06516-2770, United States

RECRUITING

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

Gainesville, Florida, 32608, United States

RECRUITING

Orlando VA Medical Center, Orlando, FL

Orlando, Florida, 32803, United States

RECRUITING

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033, United States

RECRUITING

Robley Rex VA Medical Center, Louisville, KY

Louisville, Kentucky, 40206-1433, United States

RECRUITING

Kansas City VA Medical Center, Kansas City, MO

Kansas City, Missouri, 64128, United States

RECRUITING

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

St Louis, Missouri, 63106, United States

RECRUITING

Durham VA Medical Center, Durham, NC

Durham, North Carolina, 27705, United States

RECRUITING

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

Salisbury, North Carolina, 28144, United States

RECRUITING

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97239, United States

RECRUITING

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, 29401-5799, United States

RECRUITING

Memphis VA Medical Center, Memphis, TN

Memphis, Tennessee, 38104-2127, United States

RECRUITING

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Nashville, Tennessee, 37212-2637, United States

RECRUITING

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030, United States

NOT YET RECRUITING

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

Seattle, Washington, 98108-1532, United States

RECRUITING

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, 53705-2254, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Testosterone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Robert B. Montgomery, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert B Montgomery, MD

CONTACT

(206) 277-6878; rbmontgo@uw.edu

Elahe Mostaghel, MD

CONTACT

(206) 762-1010; emostagh@fhcrc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 3 cohort phase II study

Study Record Dates

• First Submitted: August 11, 2021
• First Posted: August 18, 2021
• Study Start: August 31, 2021
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2027
• Last Updated: July 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)