Pilot Study to Assess the Potential Clinical Utility of 18F Fluciclovine PET for Cervical and Endometrial Cancer.

NCT ID: NCT03423082

Last Updated: 2020-10-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-11
• Study Completion Date: 2019-12-18

Brief Summary

18F Fluciclovine is a recently FDA- approved radiopharmaceutical for prostate cancer biochemical recurrence, which is only minimally eliminated by the kidneys and therefore the image interpretation is not affected by nonspecific urine activity in the ureters and bladder, which is advantageous for pelvic imaging. Recent literature suggests that Fluciclovine PET has diagnostic potential for a variety of solid tumors, thus, allowing new opportunities for noninvasive probing of glutamine metabolism and clinical use in patient management. Current literature indicates that amino acid transporters including that of glutamine are upregulated in endometrial and cervical cancer so that Fluciclovine PET may have clinical potentials. The hypothesis is that Fluciclovine PET provides better imaging properties and greater diagnostic confidence and accuracy than FDG PET does in pelvic malignancies.

Given the lack of current clinical data, a pilot study providing a direct comparison of Fluciclovine PET with FDG PET is warranted. The investigators seek to conduct a pilot study with 10 subjects to evaluate the clinical utility of Fluciclovine PET for staging of cervical cancer and endometrial cancer. This research will compare the diagnostic performance of the research Fluciclovine PET/MRI with the standard-of-care FDG PET/CT as an exploratory endpoint.

Detailed Description

Background:

Endometrial cancer arises from the inner lining of the uterus and is one of the most common malignancies in women, representing 3.6% of all new cancer cases in the US. It is estimated that there are more than 60,000 new cases of endometrial cancer and more than 10,000 people will die of this malignancy in 2016. It is most frequently diagnosed among women aged 55-64. Cervical cancer starts in the cervix, the lower part of the uterus. Its prevalence is lower compared with endometrial cancer thank to effective screening and early disease detection with the Pap smear. In 2016, it is estimated that there will be more than 12,000 new cases of cervical cancer and more than 4,000 patients will die of this disease in the US.

Positron Emission Tomography (PET) combined with Computed Tomography (CT) is an essential part of the workup for many malignancies. F-18 FDG PET/CT is currently the standard-of-care (SOC) PET/CT modality for staging and restaging of pelvic malignancies in women. But there are certain diagnostic limitations related to F-18 FDG because it is mainly eliminated by the kidneys and often interferes with the detection of cancer lesions, particularly in the abdominal and pelvic regions. On the other hand, the recently FDA approved F-18 Fluciclovine is only minimally eliminated by the kidneys and therefore the image interpretation is not affected by nonspecific urine activity in the ureters and bladder, which is advantageous for pelvic imaging. Recent literature suggests that Fluciclovine PET has diagnostic potential for a variety of solid tumors, thus, allowing new opportunities for noninvasive probing of glutamine metabolism and clinical use in patient management.

Current literature indicates that amino acid transporters including that of glutamine are upregulated in endometrial and cervical cancer so that Fluciclovine PET may have clinical potentials. The hypothesis is that Fluciclovine PET provides better imaging properties and greater diagnostic confidence and accuracy than FDG PET does in pelvic malignancies.

Given the lack of current clinical data, a pilot study providing a direct comparison of Fluciclovine PET with FDG PET is warranted.

Objective:

The investigators seek to conduct a pilot study to evaluate the clinical utility of Fluciclovine PET for staging of cervical cancer and endometrial cancer. This research will focus on pelvic imaging comparing the diagnostic performance of the research Fluciclovine PET/MRI with SOC FDG PET/CT as an exploratory endpoint. Dynamic PET imaging on a hybrid PET/MR scanner will provide valuable pharmacokinetic information that can be used to identify the optimal time window for the detection and characterization of the primary tumor and pelvic nodal disease. Additional abdominal imaging will allow for further correlation with FDG PET/CT in terms of nodal disease and distant metastasis detection. As previously demonstrated in prostate cancer, the Fluciclovine uptake can be heterogeneous which may have diagnostic and prognostic implications. Therefore, this pilot study will provide valuable information on potential Fluciclovine heterogeneity in cervical and uterine cancer. Textural heterogeneity of the primary will be compared between Fluciclovine and FDG PET. The initial experience gained with this pilot study will provide valuable insights into the pharmacokinetics and textural heterogeneity of Fluciclovine PET in cervical and uterine cancers, and presents the first data on the potential strengths and weaknesses of Fluciclovine PET/MR compared with FDG PET/CT.

1. The investigators hypothesize that Fluciclovine PET is non-inferior to FDG PET regarding detection of the primary tumor.

2. It is hypothesized that nodal disease staging is more accurate with Fluciclovine than with FDG PET because of the low level of nonspecific urinary bladder and ureter activity.

3. It is hypothesized that the dynamic uptake pattern of the primary lesion correlates with the tumor grading on histopathology.

4. It is hypothesized that textural heterogeneity is different between Fluciclovine and FDG PET.

Specific Aims:

• To study the pharmacokinetics of Fluciclovine PET in women with cervical and uterine cancers
• To characterize physiologic uptake pattern of the uterus and ovaries when these are not affected by tumor.
• To identify the optimal time window for the quantitative analysis of Fluciclovine primary and pelvic nodal disease
• To correlate the time-activity curve pattern of the primary lesion with histopathologic tumor grading
• To compare diagnostic performance of Fluciclovine PET and FDG PET
• To compare textural heterogeneity of the primary between Fluciclovine PET and FDG PET

Significance:

The initial experience gained with this pilot study will provide valuable insights into the pharmacokinetics, lesion detectability and textural heterogeneity of Fluciclovine PET in cervical cancer and uterine cancer. The study provides preliminary data on the potential strengths and weaknesses of Fluciclovine PET/MR compared with the SOC FDG PET/CT.

Fluciclovine PET may provide a significant improvement in the TNM staging compared with FDG PET as it is not affected by nonspecific urine activity in the ureters and bladder, which is a common diagnostic problem for FDG PET. By combining the excellent soft-tissue contrast of MRI with Fluciclovine PET, the hybrid PET/MR scanning could be a convenient and effective one-stop imaging procedure providing both pelvic TNM staging and whole-body M staging. Moreover, valuable prognostic information may be derived from Fluciclovine PET pharmacokinetics and heterogeneity assessment as well as multi-parametric PET/MR evaluation.

Conditions

Cervical Cancer; Uterine Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

18F fluciclovine PET scan

Subjects with recently biopsy-proven malignancy of the cervix or uterus undergo an 18F fluciclovine PET scan on a hybrid PET/MRI scanner after they have completed a standard-of-care F-18 FDG PET/CT study.

Group Type: EXPERIMENTAL

18F fluciclovine

Intervention Type: DRUG

Each subject will receive one IV dose of 18F fluciclovine for PET scanning

18F fluciclovine PET

Intervention Type: DEVICE

Each subject will undergo one 18F fluciclovine PET scan on a hybrid PET/MRI scanner

Interventions

18F fluciclovine

Each subject will receive one IV dose of 18F fluciclovine for PET scanning

Intervention Type: DRUG

18F fluciclovine PET

Each subject will undergo one 18F fluciclovine PET scan on a hybrid PET/MRI scanner

Intervention Type: DEVICE

Other Intervention Names

Axumin

Eligibility Criteria

Inclusion Criteria

• Female
• 18 years and older
• Biopsy-proved cervical cancer or endometrial cancer within three months of study enrollment
• Standard-of-care (SOC) FDG PET/CT exam performed within 30 days of study enrollment

Exclusion Criteria

• Female < 18 years old
• No history of cervical cancer or endometrial cancer
• Primary biopsy > 3 months of study enrollment
• Systemic therapy or radiation therapy initiated
• SOC FDG PET/CT exam performed > 30 days of study enrollment
• Therapeutic procedures (chemotherapy, radiation therapy) have been initiated
• Pregnancy or lactation
• Claustrophobia or inability to tolerate the imaging procedure on the PET/MR scanner
• Individual is not willing to give informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Blue Earth Diagnostics

INDUSTRY

Sponsor Role: collaborator

Nghi Nguyen

OTHER

Sponsor Role: lead

Responsible Party

Nghi Nguyen

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nghi C Nguyen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistant Professor of Radiology

Locations

UPMC Presbyterian - MR Research Center

Pittsburgh, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PRO17120310

Identifier Type: -

Identifier Source: org_study_id