PSMA-Directed Para-Aortic Radiation Therapy for Oligorecurrent Prostate Cancer

Phase 2

Recruiting

• Conditions: Prostate Cancer; Hormone Sensitive Prostate Cancer; Prostate Adenocarcinoma
• Interventions: Drug: Androgen Deprivation Therapy; Drug: Androgen Receptor Signaling Inhibitor

• Registration Number: NCT06392295
• Lead Sponsor: University of Miami

Brief Summary

The purpose of this prostate cancer research study is to learn about:

1. Improving control of prostate cancer using radiation therapy, delivered to the para-aortic and pelvic lymph nodes, in addition to systemic androgen suppression therapy;

2. Preserving quality of life after radiation therapy;

3. Leveraging imaging results from prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) scans to evaluate and manage disease progression.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-25
• Study First Submitted QC: 2024-04-25
• Study First Posted: 2024-04-30
• Status Verified: 2024-07
• Study Start: 2024-07-03
• Last Update Submitted: 2024-07-10
• Last Update Posted: 2024-07-12
• Primary Completion: 2027-08-01
• Study Completion: 2029-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 34

Inclusion Criteria

1. Histologically proven prostate adenocarcinoma

2. Male, ≥ 18 years old

3. Oligorecurrent disease limited to the sub-diaphragmatic region with or without pelvic lymph nodes

   • a. No more than a total of 5 lesions on PSMA PET/CT scan (each lesion defined as positive with standardized uptake value (SUV) > liver uptake and CT scan correlate)
   • b. No disease outside of the pelvic and sub-diaphragmatic para-aortic lymph nodes
   • c. At least one lesion in the sub-diaphragmatic para-aortic lymph nodes
   • d. Non-bulky nodal disease (ie, tumor <5 cm)

4. Prior pelvic radiation with disease response

   • a. Definitive radiation therapy to the prostate with or without treatment of the pelvic lymph nodes and/or
   • b. Salvage or adjuvant radiation therapy to the prostate bed following prostatectomy with or without treatment of the pelvic lymph nodes

5. Hormone-sensitive prostate cancer

6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

7. Ability to understand the investigational nature, potential risks and benefits of the research study, and willingness to sign the written informed consent and HIPAA document(s)

8. Willingness to fill out quality of life and psychosocial forms

9. Willingness to participate in our institution's Prostate Cancer Database Protocol (ID# 20090767)

Exclusion Criteria

1. No pathological diagnosis of prostate adenocarcinoma
2. Patient has more than 5 sites of metastatic disease
3. Patient has history of bone and/or visceral metastasis
4. No evidence of disease in the para-aortic lymph nodes
5. No staging with PSMA PET/CT scan
6. History of prior radiation therapy outside the pelvis for prostate cancer
7. Bulky nodal disease >5 cm in tumor size
8. Androgen deprivation therapy (ADT) or chemotherapy in the three months prior to staging PSMA PET/CT scan (suggesting oligoprogressive disease, rather than true oligorecurrent disease) or at time of study enrollment
9. Suspicious radiologic evidence of disease in the prostate on staging PSMA PET/CT scan without confirmatory negative prostate biopsy
10. Implanted hardware which limits treatment planning or delivery (determined by treating physician)
11. Castration-resistant prostate cancer (history of rising PSA with serum testosterone level <50 ng/dL)
12. Patients with ECOG performance status > 2
13. History of inflammatory bowel disease
14. History of malignancy other than prostate cancer except for non-melanoma skin cancer
15. Patients unable to consent or are prisoners
16. Unwilling to fill out quality of life and psychosocial forms
17. Participants with impaired decision-making capacity

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PSMA-Guided PA-RT Group	Androgen Deprivation Therapy	Participants in this group will undergo up to six months of systemic androgen deprivation therapy (ADT) and Androgen receptor signaling inhibitor (ARSI). During system therapy, participants will undergo five weeks of para-aortic radiation therapy. Total participation duration is up to five years.
PSMA-Guided PA-RT Group	Androgen Receptor Signaling Inhibitor	Participants in this group will undergo up to six months of systemic androgen deprivation therapy (ADT) and Androgen receptor signaling inhibitor (ARSI). During system therapy, participants will undergo five weeks of para-aortic radiation therapy. Total participation duration is up to five years.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	Up to 2 years	Progression-free survival (PFS) among participants will be assessed during treatment and clinical follow-up. PFS is defined as the time from start of treatment until any of the following: Biochemical failure, escalation of therapy, radiological evidence of disease progression or death of any cause. Radiological evidence of disease progression will be assessed by the treating physician using the Response Evaluation Criteria in prostate-specific membrane antigen (PSMA) PET/CT (RECIP) version 1.0.

Secondary Outcome Measures

Name	Time	Method
Complete Early Response Rate	Up to 2 years	The Complete Early Response rate among participants will be reported. Complete Early Response is defined as seen as on the 3-month post-PA-RT PSMA PET/CT scan using the Response Evaluation Criteria in prostate-specific membrane antigen (PSMA) PET/CT (RECIP) version 1.0; or a PSA level ≤ 0.1 ng/mL. A composite of these two evaluations will be used to determine the complete early response rate.
Median Cause Specific Survival	Up to 2 years	Median case specific survival among participants will be assessed. Median cause specific survival is defined as the time from study enrollment to death secondary to prostate cancer.
Proportion of Participants Undergoing Escalation of Therapy	Up to 2 years	The proportion of participants undergoing escalation of therapy will be reported. Escalation of therapy is defined as subsequent course of radiation therapy or change in systemic therapy (except for intolerable side effects).
Change in Quality of Life Scores: EPIC 26 Short Form	Up to 2 years	Health-related Quality of Life (HRQOL) will be measured using the Expanded Prostate Cancer Index Composite 26 Short Form (EPIC-26) to evaluate patient function and satisfaction after prostate cancer treatment. EPIC-26 is a short form version of the Expanded Prostate Cancer Index Composite, and is a validated comprehensive instrument developed to measure the health-related quality of life among men with prostate cancer. EPIC-26 consists of 26 items under 5 domains of urinary incontinence, urinary irritative/obstructive, bowel, sexual, and hormonal. Response options for each item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL.
Biochemical Failure-Free Survival (FFS)	Up to 2 years	Biochemical failure-free survival among participants will be assessed during treatment and clinical follow-up. Biochemical failure-free survival is defined as the time from study enrollment to time of biochemical failure. Biochemical failure, as adapted from the Prostate Cancer Working Group 2 (PCWG2), is defined as when prostate-specific antigen (PSA) level increases ≥ 25% and ≥ 2 ng/mL above the nadir, which is confirmed by a second value obtained three or more weeks later.
Overall Survival (OS)	Up to 2 years	Overall survival (OS) among participants will be assessed. OS is defined as the time from study enrollment to death of any cause.
Proportion of Participants Experiencing Cumulative Late Grade ≥ 2 Treatment-Related Toxicity	Up to 2 years	The proportion of participants experience late grade ≥ 2 treatment related toxicity between 90 days and two years following para-aortic radiation therapy (PA-RT) will be reported. Late toxicity is defined as Grade ≥ 2 treatment-related toxicities occurring more than 90 days after completing para-aortic radiation therapy (PA-RT). The severity of the reactions to the treatment will be assessed according to using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Change in Quality of Life Scores: IPSS	Up to 2 years	Health-related quality of life (HRQOL) will be measured using the International Prostate Symptom Score (IPSS) to evaluate patient urinary function and quality of life. There are 7 questions related to urinary function. Responses are on a scale from 0 ("not at all") to 5 ("almost always"), with higher scores indicating higher levels of urinary dysfunction. There is one quality of life question related to urinary symptoms. Responses are on a scale from 0 ("delighted") to 6 ("terrible"). Responses will be tabulated for a composite score.
Metastasis-Free Survival	Up to 2 years	Metastasis-free survival among participants will be assessed during treatment and clinical follow-up. Metastasis-free survival is defined as the time from study enrollment to clinical or radiological evidence of metastatic disease or death.
Change in Quality of Life Scores: HADS	Up to 2 years	Health-related Quality of Life (HRQOL) will be measured using the Hospital Anxiety and Depression Scale (HADS) questionnaire. The HADS is a validated instrument used to measure patient symptoms of anxiety and depression. The HADS questionnaire consists of six questions, three questions each in two domains, HADS-Anxiety and HADS-Depression. Scores in each domain range from 0-9, with higher scores representing greater levels of anxiety and depression.

Trial Locations

Locations (1)

University of Miami; 🇺🇸 Miami, Florida, United States