Mechanisms of Resistance to PSMA Radioligand Therapy

Clinicaltrials.gov ID: NCT05435495
db-list-check Status RECRUITING
b-loader Phase
b-people Age ≥ 18 Years
b-bullseye-arrow Enrollments 125

Conditions

Prostate Cancer

Summary

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.

Locations

3 locations Found with status Recruiting

Status

  • RECRUITING

Contact Person

  • Johannes Czernin, MD

Principal Investigator

  • Thomas Hope, MD

Status

  • RECRUITING

Contact Person

Principal Investigator

  • Thomas Hope, MD

Status

  • RECRUITING

Contact Person

  • Lisa Bodei, MD

Principal Investigator

  • Thomas Hope, MD

Eligibility Criteria

Inclusion Criteria:

1. Initiating treatment with Lutetium based PSMA-targeted RLT.
2. 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.
3. 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.
4. Age >=18 years.
5. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

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

Study Plan

Participants undergoing 177Lu-PSMA-617 treatment

Participants undergoing PSMA targeted radioligand therapy with at least four cycles of treatment planned will undergo the following: SPECT/CTs will be performed 24 hours after the first treatment and after the fourth treatment, a tumor biopsy will be performed prior to the first 177Lu-PSMA radioligand therapy, a blood will be drawn prior to treatment for future research, and an optional tumor biopsy and blood draw for future research, may also be obtained at time of progression.

  • PROCEDURE:

    Single-photon emission computed tomography

    Description:

    Imaging procedure
  • PROCEDURE:

    Blood Draw

    Description:

    Blood draw for future research tests (45-60 mL).
  • PROCEDURE:

    Tumor Biopsy

    Description:

    Guided biopsy of lesion

Outcome Measures

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

Timeline

  • Last Updated
    January 10, 2024
  • Start Date
    June 28, 2022
  • Today
    January 16, 2025
  • Completion Date ( Estimated )
    December 31, 2024

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