BEACON: HDR Brachytherapy, EBRT and STAD for the Treatment of Local and Pelvic Recurrence of Prostate Cancer After Radiation Therapy

Sponsor

Loyola University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03553602

Collaborator

(none)

Enrollment

Location

Arm

72.1

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of combining high-dose-rate (HDR) brachytherapy with external beam radiotherapy (EBRT) to the pelvis and 6 months of hormonal therapy, otherwise known as short term androgen deprivation therapy (STAD), as treatment for prostate cancer that has come back in the prostate and pelvic lymph nodes after prior radiotherapy. The study will examine the side effects of the treatment as well as the ability of the treatment to get rid of the cancer. This involves the placement of a radioactive material in the affected area of the prostate temporarily, and then is subsequently removed using a minimally invasive technique. Participants will also receive external radiation for 5 weeks targeting the pelvis and giving a higher dose each day to the suspicious lymph nodes on PET scan. Radiation therapy will start approximately 2 months after the start of the Androgen Deprivation Therapy (hormone therapy). The hormone therapy consists of two medications, an oral medication taken daily 2 months before starting radiation therapy until the last of the radiation therapy and an injection of a medication which is given 2 months prior to the start of radiation. Patient are then followed at specific time intervals to evaluate the treatment side effects and cancer control

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer - Recurrent	Radiation: HDR Brachytherapy + EBRT + STAD	Phase 1/Phase 2

Detailed Description

Salvage regional and local radiation is frequently utilized across multiple disease sites in oncology for patients who have failed initial radiotherapy. However, in prostate cancer, due to the concern that nodal involvement is a manifestation of widespread distant disease, this type of approach has not typically been pursued. However, with newer imaging modalities such as fluciclovine PET, PSMA pet, and C11 PET, physicians are identifying nodal disease and excluding distant disease better than they ever have before. Thus, in the modern era regional control may translate to improved long-term biochemical control, and prevent the morbidity and mortality associated with clinical progression of recurrent prostate cancer

Thus, in patients who recur both in the prostate and in the pelvic lymph nodes, treating both with radiation could result in meaningful clinical efficacy for patients-similar to other disease sites. However, there are limited data exploring the feasibility and safety of this combination. Therefore, the investigators are conducting this trial, which combines salvage HDR brachytherapy to the local recurrence of the prostate cancer with EBRT to the pelvic lymph nodes, and short-term hormonal therapy, in this group of patients. The investigators hypothesize that this approach can safely be performed without excess toxicity.

Once a patient is deemed eligible for the study and has signed the informed consent form, the patient will start hormone therapy with a LHRH Agonist medication which is an intramuscular injection which patients will receive every 3-6 months for 6 months. Within 10 days of the LHRH injection the patient must start an anti-androgen pill and will take the pill once a day until the last day of radiation. Radiation Therapy will start approximate 2 months after the start of the hormone therapy. Patients will undergo 2 implants with 1 fraction of 12 Gy delivered with each implant, scheduled 1-2 weeks apart when possible, although longer or shorter intervals are acceptable with PI approval. The implant procedure will be done under general anesthesia. Patients will also receive the external beam radiotherapy (for 5 weeks), starting before or after the brachytherapy treatment. Patients will also be asked to complete 2 short quality of life questionnaires before they receive treatment and at follow up visits. Patient will follow up with the radiation oncologist for an exam at 1 month, 3 months, 6 months and 12 months after treatment and then every 6 months for 4 more years then annually thereafter.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

BEACON - A Phase I/II Study of High-dose-rate Brachytherapy and External Beam and Short-term Androgen Deprivation COmbined for the Treatment of Men With Fluciclovine PET Pelvic Nodal Uptake in Locally Recurrent Prostate Cancer After Prior Definitive Radiotherapy

Actual Study Start Date :

May 29, 2018

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HDR Brachytherapy + EBRT + STAD Day 1: HDR Brachytherapy implant: 2 fractions of 12 Gy to prostate/ proximal SV. EBRT: 50.4 Gy in 28 fractions to the pelvic lymph nodes +/- para-aortic nodes, with SIB up to 70 Gy to the PET positive lesions. 6 months hormonal therapy(LHRH agonist and antiandrogen [until the end of radiotherapy])	Radiation: HDR Brachytherapy + EBRT + STAD HDR Brachytherapy implant: 2 fractions of 12 Gy to the prostate/ proximal SV. EBRT: 50.4 Gy in 28 fractions to the pelvic lymph nodes +/- para-aortic nodes, with SIB up to 70 Gy to the PET- positive lesions. 6 months hormonal therapy(LHRH agonist and anti-androgen[until end of radiotherapy])

Arm

Intervention/Treatment

Experimental: HDR Brachytherapy + EBRT + STAD

Day 1: HDR Brachytherapy implant: 2 fractions of 12 Gy to prostate/ proximal SV. EBRT: 50.4 Gy in 28 fractions to the pelvic lymph nodes +/- para-aortic nodes, with SIB up to 70 Gy to the PET positive lesions. 6 months hormonal therapy(LHRH agonist and antiandrogen [until the end of radiotherapy])

Radiation: HDR Brachytherapy + EBRT + STAD

HDR Brachytherapy implant: 2 fractions of 12 Gy to the prostate/ proximal SV. EBRT: 50.4 Gy in 28 fractions to the pelvic lymph nodes +/- para-aortic nodes, with SIB up to 70 Gy to the PET- positive lesions. 6 months hormonal therapy(LHRH agonist and anti-androgen[until end of radiotherapy])

Outcome Measures

Primary Outcome Measures

Toxicity rate [24 months]
The primary outcome in this study is the number of acute grade ≥3 radiation-related genitourinary and gastrointestinal toxicities as described by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria

Biopsy proven locally recurrent adenocarcinoma of the prostate after the completion of definitive radiation therapy for initially diagnosed prostate cancer.
Initial cancer diagnosis that fits these specific criteria:
Stages cT1-T3a
Nx or N0
Mx or M0
Eligible initial definitive radiotherapy modalities include:
External beam radiotherapy, with photon or proton beam therapy
Definitive Brachytherapy
Stereotactic Body Radiotherapy
Fluciclovine-positive pelvic nodes (as determined by an interpreting radiologist or nuclear medicine physician) in the pelvic nodal region (defined as the pelvic nodal regions up to the common iliac nodal region) without any evidence of lymph node involvement outside of this area or distant metastases
Candidate for hormonal therapy.
Current ECOG Performance status Scale 0-2 (Appendix D)
Current International Prostate Symptom Score (IPSS) < 20 (Appendix B)
Age >18
The patient must be medically suitable to receive general or spinal anesthesia.
AST, ALT, and alkaline phosphatase < 2 x upper institutional limit within 3 months of registration.
The patient must be able and willing to sign a study-specific written informed consent form before study entry.

Exclusion Criteria

Preregistration radiation-related GI or GU toxicity (for any reason) grade ≥ 3 as defined in CTCAE version 4.03. That is, grade ≥ 3 GU or GI toxicity after first course of radiotherapy
Treatment to a "whole pelvis" field with initial radiotherapy
Patients with distant metastases (such as to the bone, visceral organs, and lymph nodes other than the pelvic nodes including the common iliac nodes).
Patients receiving any other investigational agents.
Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, severely symptomatic congestive heart failure, cardiac arrhythmia, recent myocardial infarction in last 6 months, or psychiatric illness/social situations that could limit compliance with study requirements.
Patients who have received chemotherapy or immunotherapy within one month prior to study enrollment, other than ADT.