Randomized prospective phase III trial of 68Ga-PSMA-11 PET/CT molecular imaging for prostate cancer salvage radiotherapy planning [PSMA-SRT]

Abstract

Background: Salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence after prostatectomy offers long-term biochemical control in about 50-60% of patients. SRT is commonly initiated in patients with serum PSA levels < 1 ng/mL, a threshold at which standard-of-care imaging is insensitive for detecting recurrence. As such, SRT target volumes are usually drawn in the absence of radiographically visible disease. 68Ga-PSMA-11 (PSMA) PET/CT molecular imaging is highly sensitive and may offer anatomic localization of PCa biochemical recurrence. However, it is unclear if incorporation of PSMA PET/CT imaging into the planning of SRT could improve its likelihood of success. The purpose of this trial is to evaluate the success rate of SRT for recurrence of PCa after prostatectomy with and without planning based on PSMA PET/CT.

Methods: We will randomize 193 patients to proceed with standard SRT (control arm 1, n = 90) or undergo a PSMA PET/CT scan (free of charge for patients) prior to SRT planning (investigational arm 2, n = 103). The primary endpoint is the success rate of SRT measured as biochemical progression-free survival (BPFS) after initiation of SRT. Biochemical progression is defined by PSA ≥ 0.2 ng/mL and rising. The randomization ratio of 1:1.13 is based on the assumption that approximately 13% of subjects randomized to Arm 2 will not be treated with SRT because of PSMA-positive extra-pelvic metastases. These patients will not be included in the primary endpoint analysis but will still be followed. The choice of treating the prostate bed alone vs prostate bed and pelvic lymph nodes, with or without androgen deprivation therapy (ADT), is selected by the treating radiation oncologist. The radiation oncologist may change the radiation plan depending on the findings of the PSMA PET/CT scan. Any other imaging is allowed for SRT planning in both arms if done per routine care. Patients will be followed until either one of the following conditions occur: 5 years after the date of initiation of randomization, biochemical progression, diagnosis of metastatic disease, initiation of any additional salvage therapy, death.

Discussion: This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa early BCR following radical prostatectomy.

Acronym: PSMA-SRT Phase 3 trial.

Clinical trial registration: ■ IND#130649 ◦ Submission: 04.26.2016 ◦ Safe-to-proceed letter issued by FDA: 05.25.2016 ■ UCLA IRB #18-000484, ■ First submission: 3.27.2018 ■ Date of approval: 5.31.2018 ■ UCLA JCCC Short Title NUC MED 18-000484 ■ NCI Trial Identifier NCI-2018-01518 ■ ClinicalTrials.gov Identifier NCT03582774 ■ First Submitted: 06.19.2018 ■ First Submitted that Met QC Criteria: 06.27.2018 ■ First Posted: 07.11.2018 ■ Last Update Submitted that Met QC Criteria: 07.17.2018 ■ Last Update Posted: 07.19.2018 TRIAL STATUS: Current Trial Status Active as of 08/13/2018 Trial Start Date 09/01/2018-Actual Primary Completion Date 09/01/2023-Anticipated Trial Completion Date 09/01/2024-Anticipated.

Keywords: PET/CT; PSMA; Prostate cancer; Randomized phase 3 trial; Salvage radiation therapy.

Conflict of interest statement

Ethics approval and consent to participate

The protocol, the ICF and all forms of participant information related to the study have been reviewed and approved by the UCLA institutional review board (UCLA IRB#18–000484). Any changes made to the protocol will be submitted as a modification and will be approved by the IRB prior to implementation. All subjects must sign and personally date the IRB approved ICF after receiving detailed written and verbal information about the reason, the nature and the details of the trial prior to the initiation of any study-related procedures. This will be done according to the guidelines provided in the Declaration of Helsinki, ICH E6 Guideline for Good Clinical Practice (GCP) and government regulations, including (as applicable) the US Code of Federal Regulations Title 21 CFR 50.20 through 50.27. The subject must be made aware and agree that personal information may be reviewed during an audit by competent authorities and properly authorized persons. However, personal information will be treated as strictly confidential and will not be publicly available. The UCLA Nuclear Medicine research team will enter all data of each patient into REDCap database. Only the UCLA Nuclear Medicine research team will have access to the REDCap database (protected and encrypted access). Patients will be informed of the extent to which their confidential health information generated from this study may be used for research and publication purposes. Following this discussion, they will be asked to sign the HIPAA form and informed consent documents. The original signed document will become part of the patient’s medical records, and each patient will receive a copy of the signed document. The use and disclosure of protected health information will be limited to the individuals described in the informed consent document. ICF and HIPAA form will be given to the patient for review. Consent will be obtained after a clear and thorough discussion between the patient and the consenting physician. If the patient is from outside UCLA, he will have a phone consultation with the UCLA research team in coordination with the treating radiation oncologist to explain and discuss all the above points. Signed ICF and HIPAA form will be obtained by fax or email in this case.

Competing interests

Johannes Czernin is a founder, board member, and holds equity in Sofie biosciences and Trethera Therapeutics. Intellectual property is patented by the University of California and licensed to Sofie Biosciences and Trethera Therapeutics.

No other potential conflict of interest relevant to this article was reported.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Study Design. 68Ga-: Gallium-68; ADT: Androgen deprivation therapy; PET/CT: Positron Emission tomography/Computed Tomography; PSA: Prostate-specific antigen; PSMA: Prostate-specific membrane antigen; SRT: Salvage Radiation Therapy; SBRT: Stereotactic Body Radiation Therapy; UCLA: University of California, Los Angeles