RECRUITING

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

Conditions

Metastatic Prostate Cancer Prostatic Neoplasms

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

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

Quick Facts

Study Start:2021-08-31

Study Completion:2027-08-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05011383

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Study Contact

Robert B Montgomery, MD

CONTACT

(206) 277-6878

rbmontgo@uw.edu

Elahe Mostaghel, MD

CONTACT

(206) 762-1010

emostagh@fhcrc.org

Principal Investigator

Robert B. Montgomery, MD

PRINCIPAL_INVESTIGATOR

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

Study Locations (Sites)

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, 80045

United States

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

West Haven, Connecticut, 06516-2770

United States

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

Gainesville, Florida, 32608

United States

Orlando VA Medical Center, Orlando, FL

Orlando, Florida, 32803

United States

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033

United States

Robley Rex VA Medical Center, Louisville, KY

Louisville, Kentucky, 40206-1433

United States

Kansas City VA Medical Center, Kansas City, MO

Kansas City, Missouri, 64128

United States

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

Saint Louis, Missouri, 63106

United States

Durham VA Medical Center, Durham, NC

Durham, North Carolina, 27705

United States

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

Salisbury, North Carolina, 28144

United States

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97239

United States

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, 29401-5799

United States

Memphis VA Medical Center, Memphis, TN

Memphis, Tennessee, 38104-2127

United States

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Nashville, Tennessee, 37212-2637

United States

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030

United States

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

Seattle, Washington, 98108-1532

United States

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, 53705-2254

United States

Collaborators and Investigators

Sponsor: VA Office of Research and Development

Robert B. Montgomery, MD, PRINCIPAL_INVESTIGATOR, VA Puget Sound Health Care System Seattle Division, Seattle, WA

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-08-31

Study Completion Date2027-08-31

Study Record Updates

Study Start Date2021-08-31

Study Completion Date2027-08-31

Terms related to this study

Keywords Provided by Researchers

Prostatic Neoplasms

Additional Relevant MeSH Terms

Metastatic Prostate Cancer