Clinical Trial · NCT06329830

177Lu-PSMA, Niraparib/AA Plus Prednisone for Prostate Cancer

Overview

The purpose of this research study is to test the safety and possible side effects of Lutetium-177 (177Lu)-Prostate-Specific Membrane Antigen (PSMA)-617 along with niraparib and abiraterone acetate plus prednisone when it is given to people diagnosed with metastatic castration-resistant prostate cancer (prostate cancer that has spread to other parts of the body and does not improve with hormonal therapies) at different dose levels. Once an optimal dose is selected, the researchers want to find out what how well these treatments work to improve survival and control the growth of the tumor.

Sponsor

Baptist Health South Florida

Phase

Phase 1/2

Contacts

Rohan Garje, M.D. (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT06329830

Drug / Compound

PSMA-617

Isotope(s):

Target(s):

PSMA

Ligand Class: Small Molecules

Chelator: DOTA

Eligibility

Inclusion

While on study medication and for 4 months following the last dose of study medication, participants must agree to use condom and an adequate contraception method for partner of childbearing potential. Participants must agree not to donate sperm while on study treatment and for a minimum of 4 months following the last dose of study medication.
Life expectancy of greater than six months as determined by the treating physician
Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2
Bone marrow reserve: absolute neutrophil count (ANC) ≥ 1500 cells/microliter (uL), platelets ≥ 100,000 cells/uL, hemoglobin ≥ 9 g/dL
Pathologically enlarged lymph nodes of any distribution and/or
Metastatic disease in the bones visible on technetium-99m-MDP (methylene diphosphonate) bone scan ("bone scan") and/or
Adequate organ function:
Should have previous therapy with at least one androgen receptor pathway inhibitor in castration resistant or sensitive setting, and
Evidence of disease progression on current therapy which is based on either:
Radiologic progression: growth of known metastases or evidence of new metastases.
Visceral metastasis of any size or distribution.
Hepatic function: total bilirubin ≤ 2 × institutional upper limit of normal (ULN), for patients with known Gilbert syndrome ≤ 3 × institutional ULN is permitted. Alanine transaminase (ALT) or aspartate transaminase (AST) ≤ 3 × institutional ULN or ≤ 5 × institutional ULN if liver metastases
Renal function: estimated glomerular filtration rate (eGFR) ≥ 45 mL/min
PSA progression: based on rising values at a minimum of 1-week intervals. The minimum starting value of PSA being 1 ng/mL
Should have prior therapy with at least one line of therapy with taxane chemotherapy in castration resistant or sensitive setting
Patients must have evidence of metastatic disease with at least one of the following:
Evidence of PSMA positive disease based on PSMA positron emission tomography (PET)/computed tomography (CT) scan utilizing radiotracers F-18 piflufolastat PSMA or Ga-68 PSMA-11. PSMA positive is defined as having at least one tumor lesion with radiotracer uptake greater than normal liver. Patients will be excluded if any lesions exceeding size criteria in short axis \[organs ≥ 1 cm, lymph nodes ≥ 2.5 cm, bones (soft tissue component) ≥ 1 cm\] have uptake less than or equal to uptake in normal liver.
Able to swallow the study medication tablets whole.
Evidence of metastatic castration resistant prostate cancer with histological or cytology confirmed adenocarcinoma. This can be based on prior biopsy of prostate or metastatic disease.

Exclusion

Received an investigational intervention (including investigational vaccines) or used an invasive investigational medical device within 30 days before the planned first dose of study medication
Known allergies, hypersensitivity, or intolerance to the excipients of Nira/AA tablets.
Prior therapy with poly adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitor
Human immunodeficiency virus load \>400 copies/mL
An acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening.
Malignancy that is considered cured with minimal risk of recurrence
A transfusion (platelets or red blood cells);
Prior therapy with 177Lu-PSMA 617 therapy. Exception: prior therapy with radium 223 is allowed if last dose was ≥ 6 months from study therapy. Note that other prior radiation therapy (such as external beam radiation therapy or brachytherapy) to prostate or other metastatic sites is allowed.
Current evidence within 3 months of study consent of any of the following: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, clinically significant arterial or venous thromboembolic events (i.e., pulmonary embolism), or clinically significant ventricular arrhythmias.
Participants with known history of human immunodeficiency virus with 1 or more of the following:
Pathological finding consistent with small cell or neuroendocrine carcinoma of the prostate
Not receiving highly active antiretroviral therapy or on antiretroviral therapy for less than 4 weeks
History of adrenal dysfunction
Presence of sustained uncontrolled hypertension (systolic blood pressure \>160 mm Hg or diastolic blood pressure \>100 mm Hg). Participants with a history of hypertension are allowed, provided that blood pressure is controlled to within these limits by an antihypertensive treatment.
Hematopoietic growth factors;
Moderate or severe hepatic impairment (Class B and C per Child-Pugh classification system).
Participants who have had the following ≤ 28 days prior to enrollment
Active malignancies (i.e., progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are:
CD4 (type of white blood cell) count \<350 at screening.
Receiving antiretroviral therapy that may interfere with the study medication
Current evidence of any medical condition that would make prednisone use contraindicated.
Major surgery
Known history of active or symptomatic viral hepatitis or chronic liver disease; encephalopathy, ascites or bleeding disorders secondary to hepatic dysfunction.