Mechanisms of Resistance to PSMA Radioligand Therapy

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05435495
• Other study ID #: 19553
• Secondary ID: R01CA235741-03
• Status: Recruiting
• Start date: October 21, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2024
• Source: University of California, San Francisco
• Contact: Maya Aslam
• Phone: (415) 514-8987
• Email: Maya.Aslam[@]ucsf.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 125
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	University of California, Los Angeles	Los Angeles	California
United States	Memorial Sloan Kettering	New York	New York
United States	University of California, San Francisco	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	National Cancer Institute (NCI), Prostate Cancer Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean whole body tumor absorbed dose (WB Dose) across all metastatic lesions	The unit density sphere model will be implemented using OLINDA, a second-generation personal computer software for internal dose assessment in nuclear medicine to measure mean dose across all metastatic lesions. This approach uses the three time-point SPECT/CTs to create a whole-body dose map, which can then be segmented. Using OLINDA, the total dose to each tumor will be calculated as the integral of activity over time estimated out to 500 hours. Dose will be calculated in gray (Gy).	Up to 6 months
Primary	Median PORTOS score	PORTOS is a gene signature that predicts salvage radiation success. A PORTOS score of zero (called a "low" PORTOS) means it predicts no benefit from salvage radiotherapy. A PORTOS greater than zero (called a "high" PORTOS score) predicts a benefit from salvage radiation.	Up to 6 months