FACBC Outcomes for Post Prostatectomy

• ClinicalTrials.gov Identifier: NCT01666808
• Recruitment Status: Completed
• First Posted: August 16, 2012
• Results First Posted: August 2, 2023
• Last Update Posted: August 2, 2023
• Sponsor: Emory University
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Ashesh B Jani, Emory University

Tracking Information

• First Submitted Date: August 14, 2012
• First Posted Date: August 16, 2012
• Results First Submitted Date: April 12, 2023
• Results First Posted Date: August 2, 2023
• Last Update Posted Date: August 2, 2023
• Actual Study Start Date: September 2012
• Actual Primary Completion Date: April 18, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 2, 2022)

Failure-free Survival [ Time Frame: 3-Year post-intervention ]

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.

Original Primary Outcome Measures (submitted: August 14, 2012)

Failure-free Survival [ Time Frame: 3-Year ]

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.

Current Secondary Outcome Measures (submitted: July 24, 2023)

• Decision Changes Regarding Radiotherapy Versus no Radiotherapy [ Time Frame: Average of 1 week post-intervention ]
  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.
• Decision Changes Regarding Whole-pelvis Versus Local Fields [ Time Frame: Average of 1 week post-intervention ]
  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.
• Total Number of Decision Changes [ Time Frame: Average of 1 week post-intervention ]
  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.
• Prostate Bed Clinical Target Volume (CTV) [ Time Frame: Average of 1 month post-intervention ]
  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.
• Prostate Bed Planning Target Volume (PTV) [ Time Frame: Average of 1 month post-intervention ]
  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.
• PTV Dosimetric Endpoints [ Time Frame: Average of 1 month post-intervention ]
  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.
• Rectum Dosimetric Endpoints [ Time Frame: Average of 1 month post-intervention ]
  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.
• Bladder Dosimetric Endpoints [ Time Frame: Average of 1 month post-intervention ]
  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.
• Rate of ≥ Grade 2 GU (Genitourinary [Renal or Urinary]) Toxicity [ Time Frame: 3-Year post-intervention ]
  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.
• Rate of ≥ Grade 2 GI (Gastrointestinal) Toxicity [ Time Frame: 3-Year post-intervention ]
  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.
• Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC) GU (Genitourinary) Domain Score [ Time Frame: 3-Year post-intervention ]
  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.
• Expanded Prostate Cancer Index Composite (EPIC) GI (Gastrointestinal) Domain Score [ Time Frame: 3-Year post-intervention ]
  Patient-reported maximum gastrointestinal toxicity based on standard EPIC-CP questionnaire. Total score range 0-12. Higher score correlates with worse outcome.
• Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Score [ Time Frame: 3-Year post-intervention ]
  Patient-reported maximum sexual function toxicity based on standard EPIC-CP questionnaire. Total score range 0-12. Higher score correlates with worse outcome.
• Expanded Prostate Cancer Index Composite (EPIC) Total Score [ Time Frame: 3-Year post-intervention ]
  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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: FACBC Outcomes for Post Prostatectomy
• Official Title: Advanced Molecular Imaging With Anti-3-[18F]FACBC PET-CT to Improve the Selection and Outcomes of Prostate Cancer Patients Receiving Post-prostatectomy Radiotherapy
• Brief Summary: 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.

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
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

• Drug: FACBC
  FACBC is given intravenously prior to PET scan, radiotherapy decisions and treatment guided by PET findings
  Other Name: anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid
• Radiation: Radiation therapy
  External beam radiotherapy to prostate bed +/- pelvic lymph nodes; final dose of 66.6 Gy.
  Other Name: Intensity-modulated radiotherapy (IMRT)

Study Arms

• 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.
  Intervention: Drug: FACBC
• 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.
  Intervention: Radiation: Radiation therapy

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 15, 2019): 165
• Original Estimated Enrollment (submitted: August 14, 2012): 162
• Actual Study Completion Date: April 18, 2022
• Actual Primary Completion Date: April 18, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 95 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01666808
• Other Study ID Numbers: IRB00057680; 1R01CA169188-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ashesh B Jani, Emory University
• Original Responsible Party: Ashesh B Jani, MD, Emory University, Associate Professor & Residency Program Director
• Current Study Sponsor: Emory University
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ashesh B Jani, MD, MSEE; Emory University
• Principal Investigator: David M Schuster, MD; Emory University

• PRS Account: Emory University
• Verification Date: July 2023