FACBC Outcomes for Post Prostatectomy

Advanced Molecular Imaging With Anti-3-[18F]FACBC PET-CT to Improve the Selection and Outcomes of Prostate Cancer Patients Receiving Post-prostatectomy Radiotherapy

Investigators will perform a study with 162 patients in whom there is a strong suspicion of prostate cancer that has returned to the body after having a prostatectomy. Half of these patients will have radiotherapy decision-making and delivery per the usual routine, and half of these patients will have the radiotherapy decision and volumes guided by the FACBC test (anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3- [18F]FACBC). The major goal of the investigation is to see whether the FACBC improves the selection and the cancer control rates of post-surgery patients with a rising PSA who undergo radiotherapy.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: Radiation therapy; Drug: FACBC

Detailed Description

Prostate cancer is the most common solid tumor, with approximately 200,000 new cases diagnosed per year. Several different local therapies are available for treatment, including surgery and radiotherapy Significant advances have been made in the technical aspects of surgery and of radiotherapy which have improved both the cancer control outcomes as well as the morbidity of treatment. Despite these significant advances, approximately 30% of patients treated with definitive local therapy experience recurrent disease. Recurrent disease after prostatectomy usually manifests with rising PSA (blood test for prostate cancer). The PSA level is often of limited use in differentiating local recurrence (ie. recurrence in the prostate bed) from recurrence outside of the prostate bed ( extra-prostatic recurrence).

One PET radiotracer which has shown promise in the staging and restaging of patients with prostate carcinoma is anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-[18F]FACBC) which is a synthetic amino acid analog. FACBC demonstrated higher accuracy compared with 111Indium-capromab-pendetide in the restaging of patients with suspected recurrent prostate carcinoma.

The major goal in this proposed investigation is to use advanced molecular imaging to better guide post-prostatectomy decision making, in terms of guiding the decision to deliver radiotherapy, and in terms of the exact areas treated with radiotherapy.

Investigators will perform a study with 162 patients in whom there is a strong suspicion of prostate cancer that has returned to the body after having a prostatectomy. Half of these patients will have radiotherapy decision-making and delivery per the usual routine, and half of these patients will have the radiotherapy decision and volumes guided by the FACBC test. The major goal of the investigation is to see whether the FACBC improves the selection and the cancer control rates of post-surgery patients with a rising PSA who undergo radiotherapy.

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adenocarcinoma of the prostate, post radical-prostatectomy Detectable PSA
• ECOG/Zubrod Performance Status of 0-2
• Negative technetium 99-m MDP or F-18 PET bone scan for skeletal metastasis
• CT or MR scan of abdomen and pelvis which does not suggest presence of metastatic disease outside of the pelvis
• Willingness to undergo pelvic radiotherapy.

Exclusion Criteria:

• Contraindications to radiotherapy (including active inflammatory bowel disease or prior pelvic XRT)
• Inability to undergo anti-3-[18F]FACBC PET-CT
• Age under 18
• Metastatic disease outside of pelvis on any imaging or biopsy
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years

• Severe acute co-morbidity, defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization in the last 3 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
  • Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immunocompromised patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FACBC PET scan; A trial group in which anti-3-[18F]FACBC PET-CT is used to guide radiotherapy decisions and radiotherapy treatment volumes.	Drug: FACBC; FACBC is given intravenously prior to PET scan, radiotherapy decisions and treatment guided by PET findings; Other Names: anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid
Active Comparator: Conventional-Only Imaging; A control group whose treatment decisions will be made based on conventional imaging - bone scan and abdominopelvic CT and/or MR scan.	Radiation: Radiation therapy; External beam radiotherapy to prostate bed +/- pelvic lymph nodes; final dose of 66.6 Gy.; Other Names: Intensity-modulated radiotherapy (IMRT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure-free Survival	Definition of failure is: serum PSA value of 0.2ng/mL or more above the postradiotherapy nadir followed by another higher value, a continued rise in the serum PSA despite radiotherapy (RT), initiation of systemic therapy after completion of RT, or clinical progression.	3-Year post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decision Changes Regarding Radiotherapy Versus no Radiotherapy	Number of decision changes regarding radiotherapy versus no radiotherapy based on F-Fluciclovine PET/CT guidance. This outcome was assessed immediately after the consensus reading of the Fluciclovine PET/CT was completed by nuclear medicine, an average of 1 week post intervention.	Average of 1 week post-intervention
Decision Changes Regarding Whole-pelvis Versus Local Fields	Number of decision changes regarding whole-pelvis versus local fields. This outcome was assessed immediately after the consensus reading of the Fluciclovine PET/CT was completed by nuclear medicine, an average of 1 week post intervention.	Average of 1 week post-intervention
Total Number of Decision Changes	Total number of radiotherapy decision changes regarding radiotherapy vs no radiotherapy and regarding whole pelvis vs local fields. This outcome was assessed immediately after the consensus reading of the Fluciclovine PET/CT was completed by nuclear medicine, an average of 1 week post intervention.	Average of 1 week post-intervention
Prostate Bed Clinical Target Volume (CTV)	Absolute volume pre- vs post-PET. This outcome was assessed after radiotherapy treatment planning was completed by radiation oncology, an average of 1 month post-intervention.	Average of 1 month post-intervention
Prostate Bed Planning Target Volume (PTV)	Absolute volume were measured pre- vs post-PET. This outcome was assessed after radiotherapy treatment planning was completed by radiation oncology, an average of 1 month post-intervention.	Average of 1 month post-intervention
PTV Dosimetric Endpoints	Standard radiotherapy dosimetric endpoints used to evaluate target coverage. Planning target volume (PTV) at V100 and V110 refer to %volume of the structure receiving 100% and 110% of the prescription dose, respectively, pre and post positron emission tomography (PET). This outcome was assessed after radiotherapy treatment planning was completed by radiation oncology, an average of 1 month post-intervention.	Average of 1 month post-intervention
Rectum Dosimetric Endpoints	Standard radiotherapy dosimetric endpoints used to evaluate normal tissue doses, in this case, the rectum. V40 and V65 refer to the %volume of the structure receiving 40 Gy and 65 Gy, respectively, pre and post positron emission tomography (PET) volumes were compared. This outcome was assessed after radiotherapy treatment planning was completed by radiation oncology, an average of 1 month post-intervention.	Average of 1 month post-intervention
Bladder Dosimetric Endpoints	Standard radiotherapy dosimetric endpoints are used to evaluate normal tissue doses, in this case, the bladder. V40 and V65 refer to the %volume of the structure receiving 40 Gy and 65 Gy, respectively, pre and post positron emission tomography (PET) volumes were compared. This outcome was assessed after radiotherapy treatment planning was completed by radiation oncology, an average of 1 month post-intervention.	Average of 1 month post-intervention
Rate of ≥ Grade 2 GU (Genitourinary [Renal or Urinary]) Toxicity	Provider-reported maximum acute (<90 days Post-Intervention) and late (≥90 days and up to 3-Years post-intervention) genitourinary toxicity based on CTCAE v4.0 criteria.	3-Year post-intervention
Rate of ≥ Grade 2 GI (Gastrointestinal) Toxicity	Provider-reported maximum acute (<90 days Post-Intervention) and late (≥90 days and up to 3-Years post-intervention) gastrointestinal toxicity ≥ Grade 2 based on CTCAE v4.0 criteria.	3-Year post-intervention
Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC) GU (Genitourinary) Domain Score	Patient-reported maximum genitourinary toxicity based on standard EPIC-CP questionnaire. EPIC GU domain score has a total score range 0-12. Higher score correlates with worse outcome. EPIC GU score includes the incontinence domain score and the irritative/obstructive.	3-Year post-intervention
Expanded Prostate Cancer Index Composite (EPIC) GI (Gastrointestinal) Domain Score	Patient-reported maximum gastrointestinal toxicity based on standard EPIC-CP questionnaire. Total score range 0-12. Higher score correlates with worse outcome.	3-Year post-intervention
Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Score	Patient-reported maximum sexual function toxicity based on standard EPIC-CP questionnaire. Total score range 0-12. Higher score correlates with worse outcome.	3-Year post-intervention
Expanded Prostate Cancer Index Composite (EPIC) Total Score	Patient-reported maximum overall (genitourinary, gastrointestinal, and sexual function) toxicity based on standard EPIC-CP questionnaire. Total score range 0-60. Higher score correlates with worse outcome.	3-Year post-intervention

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ashesh B Jani, MD, MSEE, Emory University; Principal Investigator: David M Schuster, MD, Emory University

Publications and helpful links

General Publications

• Jani AB, Schreibmann E, Goyal S, Halkar R, Hershatter B, Rossi PJ, Shelton JW, Patel PR, Xu KM, Goodman M, Master VA, Joshi SS, Kucuk O, Carthon BC, Bilen MA, Abiodun-Ojo OA, Akintayo AA, Dhere VR, Schuster DM. 18F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer (EMPIRE-1): a single centre, open-label, phase 2/3 randomised controlled trial. Lancet. 2021 May 22;397(10288):1895-1904. doi: 10.1016/S0140-6736(21)00581-X. Epub 2021 May 7.
• Dhere VR, Schuster DM, Goyal S, Schreibmann E, Hershatter BW, Rossi PJ, Shelton JW, Patel PR, Jani AB. Randomized Trial of Conventional Versus Conventional Plus Fluciclovine (18F) Positron Emission Tomography/Computed Tomography-Guided Postprostatectomy Radiation Therapy for Prostate Cancer: Volumetric and Patient-Reported Analyses of Toxic Effects. Int J Radiat Oncol Biol Phys. 2022 Aug 1;113(5):1003-1014. doi: 10.1016/j.ijrobp.2022.04.005. Epub 2022 Apr 11.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Actual): April 18, 2022
• Study Completion (Actual): April 18, 2022

Study Registration Dates

• First Submitted: August 14, 2012
• First Submitted That Met QC Criteria: August 14, 2012
• First Posted (Estimated): August 16, 2012

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: IRB00057680; 1R01CA169188-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No