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

NCT ID: NCT05011383

Last Updated: 2025-07-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

51 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-31

Study Completion Date

2027-08-31

Brief Summary

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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

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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.

Conditions

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Metastatic Prostate Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

3 cohort phase II study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ATM

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

Group Type EXPERIMENTAL

High dose testosterone

Intervention Type DRUG

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

CDK12

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

Group Type EXPERIMENTAL

High dose testosterone

Intervention Type DRUG

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

CHEK2

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

Group Type EXPERIMENTAL

High dose testosterone

Intervention Type DRUG

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

Interventions

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High dose testosterone

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

Intervention Type DRUG

Other Intervention Names

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Bipolar androgen therapy

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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VA Office of Research and Development

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert B. Montgomery, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, United States

Site Status RECRUITING

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

West Haven, Connecticut, United States

Site Status RECRUITING

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

Gainesville, Florida, United States

Site Status RECRUITING

Orlando VA Medical Center, Orlando, FL

Orlando, Florida, United States

Site Status RECRUITING

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, United States

Site Status RECRUITING

Robley Rex VA Medical Center, Louisville, KY

Louisville, Kentucky, United States

Site Status RECRUITING

Kansas City VA Medical Center, Kansas City, MO

Kansas City, Missouri, United States

Site Status RECRUITING

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

St Louis, Missouri, United States

Site Status RECRUITING

Durham VA Medical Center, Durham, NC

Durham, North Carolina, United States

Site Status RECRUITING

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

Salisbury, North Carolina, United States

Site Status RECRUITING

VA Portland Health Care System, Portland, OR

Portland, Oregon, United States

Site Status RECRUITING

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, United States

Site Status RECRUITING

Memphis VA Medical Center, Memphis, TN

Memphis, Tennessee, United States

Site Status RECRUITING

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Nashville, Tennessee, United States

Site Status RECRUITING

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States

Site Status NOT_YET_RECRUITING

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

Seattle, Washington, United States

Site Status RECRUITING

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Robert B Montgomery, MD

Role: CONTACT

(206) 277-6878

Elahe Mostaghel, MD

Role: CONTACT

(206) 762-1010

Facility Contacts

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Daniel Bowles, MD

Role: primary

720-723-6498

Herta Chao, MD

Role: primary

203-937-3421

Jess D Delaune, MD

Role: primary

352-988-7504

Priya K Gopalan, MD

Role: primary

407-631-2389

Maria Ribeiro, MD

Role: primary

404-728-7680

Fred Hendler, MD

Role: primary

502-287-3515

Linda Verkruyse, MD

Role: primary

817-681-7115

Eric Knoche, MD

Role: primary

314-289-6305

Rhonda Bitting, MD

Role: primary

919-286-0411 ext. 17-5441

Michael Goodman, MD

Role: primary

704-638-9000 ext. 15038

Julie Graff, MD

Role: primary

503-220-8262

Steven Savage, MD

Role: primary

843-792-4531

Alva Weir, MD

Role: primary

901-523-8990 ext. 6853

Sally York, MD

Role: primary

615-873-6979

Anita Sabichi, MD

Role: primary

713-798-3750

Robert B Montgomery, MD

Role: primary

206-277-6878

David Kosoff, MD

Role: primary

608-256-1901

Other Identifiers

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SPLP-003-20F

Identifier Type: -

Identifier Source: org_study_id

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