Mechanisms of Resistance to PSMA Radioligand Therapy

NCT ID: NCT05435495

Last Updated: 2025-01-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

125 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-10-21

Study Completion Date

2025-12-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Prostate Cancer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Single-photon emission computed tomography

Intervention Type PROCEDURE

Imaging procedure

Blood Draw

Intervention Type PROCEDURE

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

Tumor Biopsy

Intervention Type PROCEDURE

Guided biopsy of lesion

Interventions

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Single-photon emission computed tomography

Imaging procedure

Intervention Type PROCEDURE

Blood Draw

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

Intervention Type PROCEDURE

Tumor Biopsy

Guided biopsy of lesion

Intervention Type PROCEDURE

Other Intervention Names

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SPECT/CT Biopsy

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Prostate Cancer Foundation

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas Hope, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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University of California, Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

Memorial Sloan Kettering

New York, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Maya Aslam

Role: CONTACT

(415) 514-8987

Facility Contacts

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Maya Aslam

Role: primary

415-514-8987

Role: backup

877-827-3222

Other Identifiers

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R01CA235741-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

19553

Identifier Type: -

Identifier Source: org_study_id

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