Health Trials

Study of 18F-FFNP Breast PET/MRI

ConditionBreast Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorUniversity of Wisconsin, Madison

About this trial

This clinical trial will investigate an estrogen-regulated parameter as an early measure of endocrine therapy response: progesterone receptor (PR) protein with a progestin-based radioligand, 18F-fluorofuranylnorprogesterone (18F-FFNP). The overall purpose of this research is to test the efficacy of 18F-FFNP PET/MRI for predicting response to presurgical endocrine therapy and to determine the quantitative reliability of 18F-FFNP breast PET/MRI in patients with newly diagnosed PR+ primary breast cancer.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Postmenopausal status defined by either

prior bilateral oophorectomy

age greater than or equal to 60 years of age

age less than 60 years of age and amenorrheic for 12 or more months in the absence of prior chemotherapy, tamoxifen, toremifene or ovarian suppression and FSH and estradiol in the postmenopausal range per local normal range (Group 2 only)

Disqualifiers

Inability or unwillingness to provide informed consent to the study

HER2-positive breast cancer, as defined by immunohistochemical staining 3+ OR positive by in situ hybridization (Group 2 only)

PR and Ki67 IHC slides or FFPE tissue blocks from clinical breast biopsy not available

Patients who have completed neoadjuvant chemotherapy, endocrine therapy, targeted therapy, surgical resection, or radiation for the current biopsy-proven malignancy (Group 2 only)

Trial design

Design model

Parallel

Treatments tested in this trial

  • 18F-fluorofuranylnorprogesterone

    Drug

    18F-FFNP will be given by a slow infusion (approximately 2 minutes), and the dose administered will be approximately 7 mCi.

  • Positron Emissions Tomography / Magnetic Resonance Imaging

    Device

    Breast specific PET/MRI data will be acquired using a 3T simultaneous PET/MRI scanner (Signa PET/MR, GE Healthcare)

  • Anastrozole

    Drug

    hormone based chemotherapy that reduces estrogen, 1 mg anastrozole once daily by mouth for a minimum of 14 days

  • Blood Sampling

    Other intervention

    Venous blood samples will be collected at multiple timepoints (e.g., 5, 10, 20, 30, and 45 min after 18F-FFNP injection to determine parent and metabolite fractions

  • FDA-approved gadolinium-based intravenous contrast agent

    Drug

    FDA-approved gadolinium-based intravenous contrast agent used for the MRI portion of this study

Treatment groups

53 Participants
are divided into 3 treatment groups
Group A: Group 1: Metabolite AnalysisExperimental treatment 4 interventions
Group B: Group 2: Pre-surgical TreatmentExperimental treatment 4 interventions
Group C: Group 3: Test-RetestExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Percentage change in 18F-FFNP uptake between baseline and follow-up PET/MRI scans

Tumor uptake values of 18F-FFNP will be obtained from the attenuation corrected PET component of the simultaneous breast 18F-FFNP PET/MRI research scan according to the procedures detailed in the imaging manual and the FDA IND.

Time frame
up to 4 weeks on study and up to 7 weeks on study
2

Percentage change in tumor Ki67 proliferation score, as a surrogate measure of endocrine sensitivity

Baseline Ki67 proliferation immunohistochemistry score will be obtained from the existing clinical standard-of-care breast biopsy. Post-treatment K67 proliferation immunohistochemistry score will be obtained from the surgical specimen after excision. Treatment response is defined as a reduction in Ki67 score of greater than or equal to 60 percent. Treatment nonresponse is defined as a reduction of less than 60 percent.

Time frame
up to 4 weeks on study and up to 7 weeks on study

Secondary outcomes

1

Qualitative Analysis of 18F-FFNP uptake

18F-FFNP uptake will be visually evaluated qualitatively with the following grading scale: no uptake (tumor \< background), minimal uptake (tumor = background), mild (tumor slightly \> background), moderate uptake (tumor \>\> background), and intense uptake (tumor \>\>\> background). Tumor uptake will also be dichotomized as increased (mild, moderate, or intense uptake) or absent (no uptake, minimal).

Time frame
imaging takes up to 2 hours during a visit and will take place up to 4 weeks and up to 6 weeks for the test-retest Group 3
2

Intra- and Inter-Observer Variability of Quantitative Assessment of Tumor 18F-FFNP uptake

For the test-retest portion of the clinical trial, the mixed effects model framework will be utilized to determine the intra- and interobserver variability of quantitative assessment of tumor 18F-FFNP uptake via a parametric bootstrapping approach.

Time frame
imaging takes up to 2 hours during a visit and will take place up to 4 weeks and up to 6 weeks for the test-retest Group 3
3

Quantitative Assessment of Tumor 18F-FFNP: Standardized Uptake Values (SUV)

Differences in repeatability of the different SUV measures (SUVmax, SUVpeak, and SUVmean) and their respective methods of normalization will be assessed by comparing the variances of the relative test-retest differences, using the Pitnam-Morgan test for correlated variances.

Time frame
imaging takes up to 2 hours during a visit and will take place up to 4 weeks and up to 6 weeks for the test-retest Group 3
4

Test-Retest Variability of Quantitative Assessment of Tumor 18F-FFNP uptake

For the test-retest portion of the clinical trial, the mixed effects model framework will be utilized to determine the test-retest variability of quantitative assessment of tumor 18F-FFNP uptake via a parametric bootstrapping approach.

Time frame
imaging takes up to 2 hours during a visit and will take place up to 4 weeks and up to 6 weeks for the test-retest Group 3

Other outcomes

1

Summary of Parent and Metabolite Fractions of 18F-FFNP over the course of the scan

Median and interquartile ranges will be calculated for metabolized and unmetabolized (parent) 18F-FFNP obtained from subjects undergoing venous blood sampling in the metabolite study and plotted against time.

Time frame
imaging takes up to 2 hours during a visit and will take place up to 4 weeks on study for Group 1
2

Statistical Correlation between tumor 18F-FFNP uptake with serum progesterone, 17-OH progesterone, estradiol, and corticosteroid binding globulin levels

Pearson's or Rank correlation analysis will be performed to assess the association between tumor 18F-FFNP uptake with serum progesterone, estradiol, and corticosteroid binding globulin levels. Scatter plots, correlation coefficients (rho), 95% confidence intervals, and p values will be reported.

Time frame
imaging takes up to 2 hours during a visit and will take place up to 4 weeks on study for Group 1
3

Statistical correlation between 18F-FFNP breast PET/MRI parameters and changes in PR immunohistochemistry in therapy responders and non-responders

An ANCOVA model, which will include treatment as a fixed effect and the corresponding baseline value as a covariate, and a paired t-test will be utilized to compare the change in tumor 18F-FFNP update after window treatment with change in PR immunostaining from the biopsy to surgical specimen. Means and standard errors will be presented. Least-squares means and 95% CI will be reported. Furthermore, correlation analyses will be performed to describe these associations.

Time frame
imaging takes up to 2 hours during a visit and will take place up to 4 weeks on study for Group 1, up to 4 weeks and up to 7 weeks for Group 2, and up to 4 weeks and up to 6 weeks for Group 3
4

Statistical correlation between tumor 18F-FFNP uptake with disease recurrence

If there is sufficient follow-up data for disease recurrence, the Kaplan-Meier method will be used to analyze time to disease recurrence, defined as date of imaging day until disease recurrence. Patients who do not experience disease recurrence will be censored at the date of last available follow-up. A Cox proportional hazards model will be used to evaluate the association of tumor 18F-FFNP uptake with time to disease recurrence. If there is insufficient follow-up data, descriptive statistics will be used to summarize tumor 18F-FFNP uptake for those patients with disease recurrence

Time frame
up to 5 years (long term follow up)

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Wisconsin, Madison

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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