RecruitingPhase 2NCT05011383
High Dose Testosterone for ATM, CDK12 or CHEK2 Altered Prostate Cancers
High-dose Testosterone in Men With Metastatic Castration-resistant Prostate Cancer and ATM or CDK12 Deficiency
Sponsor
VA Office of Research and Development
Enrollment
51 participants
Start Date
Aug 31, 2021
Study Type
INTERVENTIONAL
Conditions
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
Eligibility
Sex: MALEMin Age: 18 Years
Inclusion Criteria13
- 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 Criteria10
- 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
DRUGHigh dose testosterone
High dose testosterone is administered subcutaneously once monthly until progression or toxicity
Locations(17)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05011383
Related Trials
A Study of Tarlatamab for People With Prostate Cancer
NCT0711150710 locations
Study of Sipuleucel-T With or Without Continuing New Hormonal Agents in Metastatic Prostate Cancer
NCT057519412 locations
Study of AZD0516 as Monotherapy and in Combination in Participants With Metastatic Prostate Cancer
NCT0718116151 locations
Real-world Use of Lutetium (177Lu) Vipivotide Tetraxetan in China(PSMAreal CN)
NCT072902701 location
Study of AZD0754 in Participants With Metastatic Prostate Cancer
NCT0626772915 locations