Molecular Imaging of Fulvestrant Effects on Availability of ER Binding Sites

NCT01377324 | Completed Phase 2

• 1 other identifier: RUG2010-2611
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Breast Cancer

Keywords

Breast cancer; Fulvestrant; FES; PET; Positron; Emission; Tomography; Fluoroestradiol; FES-PET; Molecular Imaging; Estrogen Receptor

Outcome Measures

Primary Outcomes (2)

• Visualize and quantify changes in FES uptake in tumor lesions during fulvestrant 500mg therapy

  FES-uptake will be calculated for all tumor lesions at baseline, 1 month and 3 months. Changes between FES-uptake during fulvestrant therapy will be calculated for: * 3 months minus baseline * 3 months minus 1 month * 1 month minus baseline

  baseline; 1 month; 3 months

• To evaluate the proportion of patients with an incomplete down-regulation/occupancy of ERs as determined by FES-PET

  FES-uptake will be calculated for all tumor lesions at baseline, after 1 month and after 3 months. Incomplete down-regulation/ occupancy of ERs is defined as 1) an absolute SUV\> 1.5, and 2) a relative decrease in SUV of \<75% during fulvestrant therapy. The proportion of patients that match these criteria will be given for: * 1 month minus baseline * 3 months minus baseline

  baseline, 1 month and 3 months

Secondary Outcomes (3)

• The feasibility to quantify changes in FES-uptake in liver metastases

  baseline, 1 month and 3 months

• to correlate FES-PET results to patient and tumor response on fulvestrant therapy

  baseline, 1 month, 3 months

• Explorative analysis to correlate several factors (among which tumor burden, ER-expression, fulvestrant levels, estradiol levels, patient weight) to FES uptake will be performed.

  baseline, 1 month and 3 months

Study Arms (1)

Single arm

EXPERIMENTAL

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

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

Interventions

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

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

Single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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

You may not qualify if:

• \. 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

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713GZ, Netherlands

Location

Related Publications (3)

• 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.

  PMID: 11387350 BACKGROUND

• 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.

  PMID: 16682724 BACKGROUND

• 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.

  PMID: 20855842 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2011
• First Posted: June 21, 2011
• Study Start: May 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: May 6, 2024

Record last verified: 2024-05

Locations

NL (1)