Clinical trial NCT05435495: Mechanisms of Resistance to PSMA Radioligand Therapy
Official title: Mechanisms of Resistance to PSMA Radioligand Therapy: Radiation Resistance Versus Dose
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Prostate Cancer
Keywords: Radioligand Therapy
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Prostate Cancer Foundation
First posted: 2022-06-28
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants will be selected from patients enrolled on Lutetium based PSMA-RLTs and expected to receiving at least four cycles of PSMA-RLT

Brief 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.

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.

Primary outcomes:
measure: Mean whole body tumor absorbed dose (WB Dose) across all metastatic lesions
timeFrame: Up to 6 months
measure: Median PORTOS score
timeFrame: Up to 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
Study officials:
affiliation: University of California, San Francisco
name: Thomas Hope, MD
role: PRINCIPAL_INVESTIGATOR
References: