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

Metastatic Prostate Cancer Clinical Trial

— VA-BAT  

Official title:

High-dose Testosterone in Men With Metastatic Castration-resistant Prostate Cancer and ATM or CDK12 Deficiency

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05011383
• Other study ID #: SPLP-003-20F
• Status: Recruiting
• Phase: Phase 2
• Start date: August 31, 2021
• Est. completion date: August 31, 2027

Study information

• Verified date: August 2023
• Source: VA Office of Research and Development
• Contact: Robert B Montgomery, MD
• Phone: (206) 277-6878
• Email: rbmontgo[@]uw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

This is an unblinded, three cohort phase II study evaluating the efficacy of high dose testosterone (BAT) for patients with mCRPC and inactivating mutations in ATM, CDK12 or CHEK2. Patients will receive BAT until disease progression or intolerance, whichever occurs first. Throughout the study, safety and tolerability will be assessed by frequent recording of adverse events, vital signs and safety laboratory assessments. Progression will be evaluated with bone scan, CT of the abdomen/pelvis and PSA as per PCWG3 criteria.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 51
• Est. completion date: August 31, 2027
• Est. primary completion date: August 31, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Prostate Cancer
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Rocky Mountain Regional VA Medical Center, Aurora, CO	Aurora	Colorado
United States	Ralph H. Johnson VA Medical Center, Charleston, SC	Charleston	South Carolina
United States	Atlanta VA Medical and Rehab Center, Decatur, GA	Decatur	Georgia
United States	Durham VA Medical Center, Durham, NC	Durham	North Carolina
United States	North Florida/South Georgia Veterans Health System, Gainesville, FL	Gainesville	Florida
United States	Michael E. DeBakey VA Medical Center, Houston, TX	Houston	Texas
United States	Kansas City VA Medical Center, Kansas City, MO	Kansas City	Missouri
United States	Robley Rex VA Medical Center, Louisville, KY	Louisville	Kentucky
United States	Memphis VA Medical Center, Memphis, TN	Memphis	Tennessee
United States	Tennessee Valley Healthcare System Nashville Campus, Nashville, TN	Nashville	Tennessee
United States	Orlando VA Medical Center, Orlando, FL	Orlando	Florida
United States	VA Portland Health Care System, Portland, OR	Portland	Oregon
United States	St. Louis VA Medical Center John Cochran Division, St. Louis, MO	Saint Louis	Missouri
United States	Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC	Salisbury	North Carolina
United States	VA Puget Sound Health Care System Seattle Division, Seattle, WA	Seattle	Washington
United States	VA Connecticut Healthcare System West Haven Campus, West Haven, CT	West Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PSA response	PSA response as measured by a 50% decline from baseline maintained for 12 weeks	12 weeks