Molecular Imaging of Fulvestrant Effects on Availability of ER Binding Sites

NCT ID: NCT01377324

Last Updated: 2024-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2013-08-31

Brief Summary

The dose of fulvestrant to optimally downregulate estrogen receptors (ER) is currently subject of debate. Effects of fulvestrant on the ERs may be evaluable by molecular imaging using positron emission tomography with the ER-specific FES tracer. In this pilot study we will evaluate the effects of the new dose of fulvestrant (500mg i.m.)on the availability of ER binding sites in 15 metastatic breast cancer patients.

Detailed Description

The estrogen receptor (ER) is expressed in approximately 70% of the breast carcinomas. In these patients signaling via the ER induces proliferation and cell survival of malignant cells. Fulvestrant can inhibit this signaling route by blocking the receptor and decreasing ER-expression by increasing its turn-over rate.

The historical standard dose of fulvestrant was 250mg every 28 days i.m.; however studies performing serial biopsies showed that ER-downregulation was suboptimal. Recently the standard dose has been set to 500mg i.m. on day 1; 14; 28 and every 28 days thereafter. Although slightly more effective than the 250mg dose, still questions remain with respect to the required dose to establish maximal downregulation of ER-signaling.

Immunohistochemistry only provides static information, i.e. the level of ER-expression. However, dynamic information evaluating the effects of fulvestrant on occupancy of ERs, may also be valuable.

Whole-body imaging of the availability of ER binding sites using FES-PET may prove valuable to evaluate the effects of fulvestrant on the ER non-invasively in individual patients. This potentially allows adjustment of dosing in individual patients to aid therapy efficacy.

In this pilot-study we will evaluate 15 metastatic breast cancer patients. All patients will undergo FES-PET/CT at baseline, FES-PET after 1 month, and FES-PET/CT after three months. Hormone- and fulvestrant levels will be measured in all patients. Whenever possible, tumor biopsies will be performed to correlate to FES-PET results.

Conditions

Metastatic Breast Cancer

Study Design

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

Study Groups

Single arm

Fluoroestradiol-PET is performed at baseline, after 1 month, and 3 months

Group Type: EXPERIMENTAL

Diagnostic intervention: Positron Emission Tomography with 16-alpha-[18-fluoro]-17betaestradiol

Intervention Type: OTHER

A FES-PET/(CT) will be performed thrice during protocol execution. Patients will be injected with \~200MBq 18F-FES

Interventions

Diagnostic intervention: Positron Emission Tomography with 16-alpha-[18-fluoro]-17betaestradiol

A FES-PET/(CT) will be performed thrice during protocol execution. Patients will be injected with \~200MBq 18F-FES

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 1. Patients with a history of histological proven ER-positive primary breast cancer and, whenever available, histological proven ER-positive recurrence. 2. Post-menopausal status (age ≥ 45 years with amenorrhea for > 12 months or prior bilateral ovariectomy 3. Documentation of a negative pregnancy test must be available for women less than 2 years after menopause 4. Progressive disease after 2 lines of hormonal therapy 5. No previous fulvestrant treatment 6. ER-antagonists should be discontinued for 5 weeks prior to FES-PET to prevent false negative FES-PET results. The use of aromatase inhibitors is allowed 7. ECOG performance status 0, 1 or 2 8. Life expectancy > 3 months 9. Creatinine clearance ≥ 30 ml/min 10. Age ≥ 18 years 11. Signed written informed consent 12. Able to comply with the protocol

Exclusion Criteria

• 1. Evidence of central nervous system metastases 2. Presence of life-threatening visceral metastases 3. > 3 lines of endocrine therapy for metastatic disease 4. > 2 lines of chemotherapy in metastatic disease

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

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Medical Center Groningen

Groningen, , Netherlands

Countries

Netherlands

References

Mortimer JE, Dehdashti F, Siegel BA, Trinkaus K, Katzenellenbogen JA, Welch MJ. Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol. 2001 Jun 1;19(11):2797-803. doi: 10.1200/JCO.2001.19.11.2797.

Reference Type: BACKGROUND

PMID: 11387350 (View on PubMed)

Linden HM, Stekhova SA, Link JM, Gralow JR, Livingston RB, Ellis GK, Petra PH, Peterson LM, Schubert EK, Dunnwald LK, Krohn KA, Mankoff DA. Quantitative fluoroestradiol positron emission tomography imaging predicts response to endocrine treatment in breast cancer. J Clin Oncol. 2006 Jun 20;24(18):2793-9. doi: 10.1200/JCO.2005.04.3810. Epub 2006 May 8.

Reference Type: BACKGROUND

PMID: 16682724 (View on PubMed)

Howell A, Bergh J. Insights into the place of fulvestrant for the treatment of advanced endocrine responsive breast cancer. J Clin Oncol. 2010 Oct 20;28(30):4548-50. doi: 10.1200/JCO.2010.30.6266. Epub 2010 Sep 20. No abstract available.

Reference Type: BACKGROUND

PMID: 20855842 (View on PubMed)

Other Identifiers

RUG2010-2611

Identifier Type: -

Identifier Source: org_study_id