Mechanisms of Resistance to PSMA Radioligand Therapy

Official title

Mechanisms of Resistance to PSMA Radioligand Therapy: Radiation Resistance Versus Dose

Overview

This is a multicenter, correlative study to existing Lutetium based prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) trials and uses.

Detailed description

PRIMARY OBJECTIVES:

I. To determine the relationship between whole body tumor absorbed dose and response Lutetium based prostate-specific membrane antigen-targeted radioligand therapy (177Lu-PSMA-RLT).

II. To determine the relationship between Post-Operative Radiation Therapy Outcomes Score (PORTOS) score and response to 177Lu-PSMA-RLT.

III. To determine the relative importance of radiation dose (whole body tumor absorbed dose) and radiation sensitivity (PORTOS score) as a marker of response to 177Lu-PSMA-RLT.

EXPLORATORY OBJECTIVES:

I. To develop novel signature of radiation sensitivity.

II. To evaluate tumor biopsies to understand mechanisms of resistance.

III. To understand utility of post-cycle 4 single-photon emission computed tomography (SPECT/CT) to evaluate treatment response.

Study participants will undergo a biopsy and blood draw prior to the initiation of planned therapy, as well as SPECT/CT imaging performed after the first and fourth treatments. One SPECT/CT scan will be performed 24 (+/- 6) after the first treatment, and after the fourth treatment, a 24 +/- 6-hour post-treatment SPECT/CT will be performed. Additionally, study participants may choose to undergo optional biopsy and blood draw at time of progression.

Interventions

• Procedure Single-photon emission computed tomography
  Imaging procedure
• Procedure Blood Draw
  Blood draw for future research tests (45-60 mL).
• Procedure Tumor Biopsy
  Guided biopsy of lesion

Primary outcome measures

• Mean whole body tumor absorbed dose (WB Dose) across all metastatic lesions [Time frame: Up to 6 months]
• Median PORTOS score [Time frame: Up to 6 months]

Eligibility criteria

Inclusion criteria

• Initiating treatment with Lutetium based PSMA-targeted RLT.
• Participants must have a PSMA-avid lesion that is accessible to biopsy. Biopsy of newly emerging radiographic metastases is desired and preferable to the biopsy of previously existing lesions whenever possible. Newly emerging lesions are defined as those that are absent on a previous scan, or those demonstrating unequivocal progression since initiation of the last treatment. Biopsies will be performed according to local institutional standards.
• Patients on warfarin, aspirin, or other anti-coagulants are eligible provided they are deemed able to tolerate discontinuation of anti-coagulation for at least five days prior to the biopsy. Conversion to low molecular weight heparin prior to biopsy is permitted per local standard operating procedures, provided there is approval by the interventional radiologist or the PI.
• Age >=18 years.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

• Patients with significant congenital or acquired bleeding disorders (eg von Wildebrand's disease, acquired bleeding factor inhibitors).
• Patients who are not able to undergo additional study related imaging procedures.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 3 centers

• University of California, Los Angeles — Los Angeles
• University of California, San Francisco — San Francisco
• Memorial Sloan Kettering — New York

Identifiers

NCT: NCT05435495 · 19553 · R01CA235741-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗