Study of 18F-FFNP Breast PET/MRI

Official title

Phase II Study of 18F-FFNP Breast PET/MRI in the Assessment of Early Response of Breast Cancer to Presurgical Endocrine Therapy

Overview

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.

Detailed description

Primary Objective

• Determine the diagnostic accuracy of 18F-FFNP PET/MRI for predicting response to presurgical endocrine therapy.

Secondary Objectives

* Determine the repeatability of quantitative assessment of tumor 18F-FFNP uptake. * Determine the intra- and inter-observer variability of quantitative assessment of tumor 18F-FFNP uptake. * Assess the safety and tolerability of 18F-FFNP.

Exploratory Objectives

* Define the parent and metabolite fractions of 18F-FFNP over the time course of the scan. * Assess the association between tumor 18F-FFNP uptake with serum progesterone, estradiol, and corticosteroid binding globulin levels. * Compare changes in 18F-FFNP breast PET/MRI parameters with changes in PR immunohistochemistry in therapy responders and non-responders. * Assess the association between tumor 18F-FFNP uptake with disease recurrence. * Determine whether MRI parameters improve the predictive value of FFNP PET alone.

Interventions

• Drug 18F-fluorofuranylnorprogesterone
  18F-FFNP will be given by a slow infusion (approximately 2 minutes), and the dose administered will be approximately 7 mCi.
• Device Positron Emissions Tomography / Magnetic Resonance Imaging
  Breast specific PET/MRI data will be acquired using a 3T simultaneous PET/MRI scanner (Signa PET/MR, GE Healthcare)
• Drug Anastrozole
  hormone based chemotherapy that reduces estrogen, 1 mg anastrozole once daily by mouth for a minimum of 14 days
• Other Blood Sampling
  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
• Drug FDA-approved gadolinium-based intravenous contrast agent
  FDA-approved gadolinium-based intravenous contrast agent used for the MRI portion of this study

Primary outcome measures

• Percentage change in 18F-FFNP uptake between baseline and follow-up PET/MRI scans [Time frame: up to 4 weeks on study and up to 7 weeks on study]
• Percentage change in tumor Ki67 proliferation score, as a surrogate measure of endocrine sensitivity [Time frame: up to 4 weeks on study and up to 7 weeks on study]

Secondary outcome measures (5)

• Qualitative Analysis of 18F-FFNP uptake [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]
• Intra- and Inter-Observer Variability of Quantitative Assessment of Tumor 18F-FFNP uptake [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]
• Quantitative Assessment of Tumor 18F-FFNP: Standardized Uptake Values (SUV) [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]
• Test-Retest Variability of Quantitative Assessment of Tumor 18F-FFNP uptake [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]
• NCIC Adverse Events Version 5.0 Frequency Tables [Time frame: up to 7 weeks]

Eligibility criteria

Inclusion criteria

• 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)
• Diagnosis of biopsy-proven invasive breast cancer measuring at least 1.0 cm in diameter by any imaging modality. Malignancy may be located within the breast, axilla (e.g. metastatic axillary lymph node), or both the breast and axilla
• Biopsy-proven PR-positive invasive breast cancer
• Definitive surgical excision of the primary tumor planned without neoadjuvant therapy; defined as therapy (chemotherapy, targeted therapy, radiation therapy or endocrine therapy) given to decrease the size of the tumor prior to planned surgery. (Group 2 only)

Exclusion criteria

• 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)
• Patients who are planning to undergo anastrozole as standard of care neoadjuvant therapy
• Patients who are currently taking aromatase inhibitors or ER antagonists (tamoxifen, raloxifene)
• Patients with breast expanders
• Patients who are pregnant or lactating
• Patients with clinical contraindication for use of aromatase inhibitors (AI) while on study as determined by investigator (Group 2 only)
• Patients with a contraindication to gadolinium-based contrast agents, including allergy or impaired renal function (per UW Health Guidelines)
• Patients with a history of allergic reaction attributable to compounds of similar chemical or biologic composition to 18F-FFNP
• Patients with history of allergic reaction to anastrozole (Group 2 only)
• Patients in liver failure as judged by the patient's physician
• Patients with standard contraindications to MRI (per UW Health Guidelines)
• Patients requiring conscious sedation for imaging are not eligible; patients requiring mild, oral anxiolytics for the clinical MRI scan will be allowed to participate as long as the following criteria are met:

• The patient has their own prescription for the medication
• The informed consent process is conducted prior to the self-administration of the medication.
• The patient comes to the research visit with a driver.
• Patients unable to lie prone for 45 minutes for imaging

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 1 center

• UW Carbone Cancer Center — Madison

Identifiers

NCT: NCT06086704 · 2023-1114 · Protocol Version 7/30/2024 · SMPH/RADIOLOGY/RADIOLOGY · UW23020 · 1R01CA272571-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗