18Fluorine-Fluciclovine PET/CT for Staging Muscle Invasive Bladder Cancer Preceding Radical Cystectomy

• ClinicalTrials.gov Identifier: NCT04018053
• Recruitment Status: Active, not recruiting
• First Posted: July 12, 2019
• Last Update Posted: January 23, 2024
• Sponsor: Dana-Farber Cancer Institute
• Collaborator: Blue Earth Diagnostics
• Information provided by (Responsible Party): Heather A. Jacene, MD, Dana-Farber Cancer Institute

Tracking Information

• First Submitted Date: July 10, 2019
• First Posted Date: July 12, 2019
• Last Update Posted Date: January 23, 2024
• Actual Study Start Date: February 26, 2020
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 10, 2019)

The agreement rate of metastatic disease status between 18F-fluciclovine-PET/CT and histopathology from radical cystectomy [ Time Frame: 2 years ]

Lymph nodes will be classified as positive or negative for metastatic disease on 18F-fluciclovine PET/CT and compared to pathologic stage as determined from surgery.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 10, 2019)

• The amount of 18F-fluciclovine accumulation in the primary bladder tumor on PET [ Time Frame: 2 years ]
  18F-fluciclovine SUVmax in primary bladder tumor as a measure of uptake; primary tumor stage and size at radical cystectomy
• The rate of detection of suspected distant metastatic disease by 18F-fluciclovine-PET/CT [ Time Frame: 2 years ]
  Visualization of distant metastases on 18F-fluciclovine-PET/CT will be binary-categorized as present/absent. We will compute sensitivity to compare 18F-fluciclovine-PET/CT with standard imaging modalities for distant metastases. The number of distant metastases will be descriptively shown by imaging modalities.
• 18F-fluciclovine uptake on PET/CT to the presence/absence of ASCT2 and LAT1 amino acid transporters. [ Time Frame: 2 Years ]
  18F-fluciclovine SUVmax in primary bladder tumor; Presence/absence of ASCT2 and LAT1 amino acid transporter in resected primary bladder tumors

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

Descriptive Information

• Brief Title: 18Fluorine-Fluciclovine PET/CT for Staging Muscle Invasive Bladder Cancer Preceding Radical Cystectomy
• Official Title: A Pilot Study of 18Fluorine-Fluciclovine Positron Emission Tomography/Computed Tomography for Staging Muscle Invasive Bladder Cancer Preceding Radical Cystectomy
• Brief Summary: This research study is studying a positron emission tomography (PET) agent called 18F-fluciclovine to evaluate how well 18F-fluciclovine-PET scans determine the extent of muscle invasive bladder cancer (as compared to regular CT and MRI imaging) and whether 18F-fluciclovine-PET scans can provide information about the pathologic grade of the tumor.

Detailed Description

This research study is a pilot study, which is the first-time investigators are examining this study imaging agent, 18F-fluciclovine, for use in imaging bladder cancer.

Staging of muscle invasive bladder cancer is currently done using computed tomography (CT) and/or magnetic resonance imaging (MRI). Both CT and MRI are useful to determine the extent of bladder cancer, but some studies show that up to 40% of patients with negative CT or MRI scans for disease outside the bladder are found to have disease outside the bladder (in lymph nodes near the bladder) at the time of surgery.

Given the limitations of the imaging exams currently used for staging bladder cancer, new techniques and imaging agents that can better identify metastatic lesions, especially within the pelvis, are desired and would be very useful.

18F-fluciclovine is a new radiotracer that was recently approved to evaluate lesions in recurrent prostate cancer (but not for bladder cancer). This radiotracer targets amino-acid receptors, which are overexpressed in multiple cancers. Studies have shown that 18F-fluciclovine PET/CT can visualize other types of cancers, such as breast cancer. A major advantage of 18F-fluciclovine is that it does not get into the bladder during the time of imaging. This may make it easier to see disease in the pelvis that is outside the bladder.

The purpose of this study to determine whether 18F-fluciclovine PET/CT can better stage muscle invasive bladder cancer compared to conventional CT or MRI. A secondary aim of this study is to determine whether 18F-fluciclovine PET/CT can reveal the pathologic grade of the bladder cancer, which is only determined from pathology specimens obtained at surgery.

• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic

Condition

• Bladder Cancer
• Urothelial Carcinoma

Intervention

• Drug: 18F-fluciclovine
  18F-fluciclovine is a new radiotracer. This radiotracer targets amino-acid transporters, which are overexpressed in multiple cancers.
  Other Name: Axumin
• Device: PET/CT
  Positron emission tomography/computed tomography (PET/CT) uses small amounts of radioactive materials called radiotracers, a special camera and a computer to help evaluate organ and tissue functions.

Study Arms

Experimental: 18F-fluciclovine

• 18F-fluciclovine will be administered via slow push over 10 seconds through a peripheral intravenous line
• Immediately after the injection of the radiopharmaceutical, dynamic PET/CT images of the pelvis will be obtained for 15 minutes
• Subsequently, PET/CT images will be obtained from the pelvis to the base of skull.

Interventions:

• Drug: 18F-fluciclovine
• Device: PET/CT

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: July 10, 2019): 16
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 30, 2024
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants must have histologically or cytologically confirmed urothelial carcinoma of the bladder.
• Participants must have cT2-T4N0 disease at the time of the study, as defined by conventional CT or MRI imaging. Patients must have no definite evidence of locoregional or distant metastatic disease at the time of study eligibility, as defined by conventional imaging.
• Radical cystectomy must be planned for the patient after the planned 18F-fluciclovine-PET/CT.
• Patients may or may not have had prior neoadjuvant therapy prior to this study.
• Age ≥18 years. Since no dosing or adverse event data are currently available on the use of 18F-fluciclovine in participants <18 years of age, and the majority of bladder cancer occur in the adult population [42], children are excluded from this study but will be eligible for future pediatric trials.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Ability and willingness to comply with the study procedures.
• The effects of 18F-fluciclovine on the developing human fetus are unknown. For this reason and because radiopharmaceuticals may be teratogenic, women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for 24 hours after the PET/CT scan is completed. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Participants with other known malignancies that has required treatment in the past 3 years.
• Pregnant women are excluded from this study because 18F-fluciclovine is a radiopharmaceutical with the potential for teratogenic effects. Because of the radiation exposure to a nursing infant from 18F-fluciclovine, women who are breastfeeding are also excluded from this study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 18F-fluciclovine.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Contraindications for PET/CT including:

  • Severe claustrophobia
• Any past or current condition that in the opinion of the study investigators would confound the results of the study or pose additional risk to the patient by their participation in the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (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: NCT04018053
• Other Study ID Numbers: 19-208
• 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: Yes
• Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: BCH - Contact the Technology & Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

• Current Responsible Party: Heather A. Jacene, MD, Dana-Farber Cancer Institute
• Original Responsible Party: Heather A. Jacene, Dana-Farber Cancer Institute, Principal Investigator
• Current Study Sponsor: Dana-Farber Cancer Institute
• Original Study Sponsor: Same as current
• Collaborators: Blue Earth Diagnostics

Investigators

• Principal Investigator: Heather Jacene, MD; Dana-Farber Cancer Institute

• PRS Account: Dana-Farber Cancer Institute
• Verification Date: January 2024