TheranosticTrials.org

Clinical Trial · NCT07860554

Pluvicto for the Treatment of African American Men With Metastatic Castration-Resistant Prostate Cancer

Overview

This phase II trial tests how well Pluvicto works in treating African American patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that has continued to grow and spread despite the surgical removal of the testes or medical intervention to block androgen production (castration-resistant). Pluvicto is a targeted radioligand therapy. It works like a guided missile, combining tumor seeking molecules with a radioactive isotope. It circulates through the bloodstream, binds to a protein on prostate cancer cells called prostate specific membrane antigen, and destroys them using radiation. Pluvicto is approved by the Food and Drug Administration for the treatment of metastatic castration-resistant prostate cancer. This trial may help researchers determine the safety and efficacy of Pluvicto specifically in African American patients with metastatic castration-resistant prostate cancer.

Sponsor

Emory University

Phase

Phase 2

Contacts

Wilena Session (CONTACT)

wsessio@emory.edu

404-778-3448

Jacob E Berchuck, MD (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT07860554

Drug / Compound

PSMA-617

Isotope(s):
Target(s):
  • PSMA
Ligand Class: Small Molecules
Chelator: DOTA

Eligibility

Inclusion

  • Participants must have progressed only once on prior second generation androgen receptor-directed therapy (ARDT) (abiraterone, enzalutamide, darolutamide, or apalutamide)
  • Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Second generation ARDT must be the most recent therapy received
  • Participants must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:
  • Progression of bone disease: two new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria \[Scher et al 2016\])
  • Estimate glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73m\^2 using the Modification of Diet in Renal Disease (MDRD) equation
  • Participants must have the ability to understand and comply with institutional radiation safety requirements
  • Participants must self-identify as being African-American
  • Participants must have the ability to understand and comply with all protocol requirements
  • Albumin ≥ 2.5 g/dL
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3.0 x ULN OR ≤ 5.0 x ULN for participants with liver metastases
  • Participants must have recovered to ≤ grade 2 from all clinically significant toxicities related to prior therapies (i.e. prior chemotherapy, radiation, etc.) except alopecia
  • Soft-tissue progression defined (Prostate Cancer Working Group Scher Prostate Cancer 2016 Oncology Response Criteria \[PCWG3\]-modified Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\]1.1 \[Eisenhauer et al 2009, Scher et al 2016\])
  • Total bilirubin \< 2 x the institutional upper limit of normal (ULN). For participants with known Gilbert's syndrome ≤ 3 x ULN is permitted
  • Participants have PSMA-positive disease on PSMA scan
  • Participants must have histological pathological, and/or cytological confirmation of adenocarcinoma of the prostate
  • First generation androgen receptor inhibitor therapy (e.g. bicalutamide) is allowed but not considered as prior ARDT therapy
  • Candidates for change in ARDT as assessed by the treating physician
  • Participants must have a castrate level of serum/plasma testosterone (\< 50 ng/dL or \< 1.7 nmol/L)
  • Participants cannot have previously progressed nor had intolerable toxicity to both enzalutamide and abiraterone
  • Serum/plasma PSA progression defined as 2 increases in PSA measured at least 1 week apart. The minimal start value is 2.0 ng/mL; 1.0 ng/mL is the minimal starting value if confirmed rise in PSA is the only indication of progression
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
  • Participants must have ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to randomization
  • Platelets ≥ 100 x 10\^9/L
  • Hemoglobin ≥ 9 g/dL

Exclusion

  • Previous treatment with any of the following within 6 months of enrollment: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation
  • Prior treatment with cytotoxic chemotherapy for castration resistant or castrate sensitive prostate cancer (e.g., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy (including monoclonal antibodies). (Note: Taxane exposure \[maximum 6 cycles\] in the adjuvant or neoadjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neoadjuvant therapy. Prior treatment with sipuleucel-T is allowed)
  • History of familial long QT syndrome or known family history of Torsades de Pointe
  • Transfusion or use of bone marrow stimulating agents for the sole purpose of making a subject eligible for study inclusion
  • A superscan as seen in the baseline bone scan, defined as 99mTc bone scintigraphy pattern demonstrating diffuse, confluent, and intense radiotracer uptake throughout the majority of the axial and appendicular skeleton, with markedly reduced or absent renal visualization and minimal soft tissue activity
  • Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar classes
  • Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: Participants with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (including \[incl.\] pads, drainage) are allowed
  • History or current diagnosis of the following electrocardiography (ECG) abnormalities indicating significant risk of safety for study participants:
  • Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
  • HIV-infected participants who are at a low risk of AIDS-related outcomes may participate in this trial
  • Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, poly (adenosine diphosphate \[ADP\]-ribose) polymerase (PARP) inhibitor, biological therapy, or investigational therapy
  • Any investigational agents within 28 days prior to day of randomization
  • Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)
  • Concurrent serious (as determined by the principal investigator) medical conditions, including, but not limited to New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation
  • Eligible for treatments other than ARDT based on presence of any mutations or biomarkers that are known as predictors of better response (e.g., AR-V7 or BRCA)
  • Not able to understand and to comply with study instructions and requirements
  • History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
  • Cardiac or cardiac repolarization abnormality, including any of the following: history of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to starting study treatment
  • Previous PSMA-targeted radioligand therapy is not allowed
  • Participants with a history of central nervous system (CNS) metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with CNS metastases are eligible if received therapy (surgery, radiotherapy, gamma knife), asymptomatic and neurologically stable without corticosteroids. Participants with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired
  • Any condition that precludes raised arms position