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NCT05011383PHASE2Recruiting

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

VA Office of Research and Development

Start Date

8/31/2021

Completion Date

8/31/2027

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

Detailed 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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

High dose testosterone

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Conditions

Metastatic Prostate Cancer

Locations

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

St 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