IMaging PAtients for Cancer Drug selecTion - Metastatic Breast Cancer

NCT01957332 | Active Not Recruiting DMC

• 1 other identifier: IMPACT MBC
• Study Type: interventional
• Target: 217
• Locations: 1 country
• Sites: 3

Brief Summary

Current patient work-up, including conventional imaging and pathological assessment of just one single biopsy, might be insufficient to identify metastatic breast cancer patients, who possibly benefit from first-line anti-hormonal or anti-HER2 therapy. As receptor conversion of the tumor is found quite frequently and molecular heterogeneity can occur within one patient, up-to-date whole body information is necessary to determine estrogen receptor (ER) and/or human epidermal growth factor receptor 2 (HER2) receptor status and subsequently guide therapy decision. With molecular imaging via PET this information can be obtained in a non-invasive, patient friendly way. Furthermore, to improve and individualize treatment and be able to identify (new) drug targets and biomarkers, sampling of venous blood, circulating tumor cells (CTC), as well as circulating tumor DNA, microRNA (miRNA) and molecular characterization of one metastasis at the beginning and, if feasible, of an additional biopsy during therapy, is necessary.

Conditions

Metastatic Breast Cancer

Keywords

molecular imaging; HER2-PET; 89Zr-trastuzumab; FES-PET; metastatic breast cancer; clinical utility

Outcome Measures

Primary Outcomes (1)

• Clinical utility

  The primary objective is to evaluate the clinical utility of experimental PET scans, in the setting of MBC at first presentation. These scans include Fluor-18-16 alpha-fluoroestradiol(18F-FES)-PET and Zirconium-89(89Zr)-trastuzumab-PET scans at baseline, and 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose(18F-FDG)-PET for early response measurement. Clinical utility in this setting might be defined as improved personalized medicine, when the PET scans show improved predictive value for therapy response in comparison or in addition to currently available clinical information including a biopsy. But also when the PET scans would have the same predictive value for therapy response compared to a biopsy, they would have clinical utility because they are less invasive and more patient friendly. The inherent focus (the primary endpoint) of this study is therefore therapy response. Therapy response will be related to the novel PET scans, both per patient and per metastasis analysis.

  3-5 years (End of study)

Secondary Outcomes (9)

• Correlation PET scans & progression-free survival (PFS)

  3-5 years (End of study)

• Correlation of DNA and RNA analyses to imaging, molecular analyses and follow-up data

  3-5 years (End of study)

• Correlation miRNA analysis to molecular analyses, imaging & clincal follow-up data

  3-5 years (End of study)

• Correlation of peptide profiling to all other molecular, imaging and clinical follow-up data

  3-5 years (EoS)

• Correlation of standard pathology results to all molecular, imaging and clinical follow up data.

  3-5 years (EoS)

Study Arms (1)

Molecular imaging

EXPERIMENTAL

All patients receive 18F-FES (\~200MBq) injection followed by a FES-PET. On the same day or the day after 18F-FES injection 89Zr-trastuzumab (\~37 MBq) will be injected. The HER2-PET will be performed 4 days after tracerinjection.

Procedure: Molecular imaging

Interventions

Molecular imaging PROCEDURE

On the day of FES-injection\&scan or the day after FES-injection, 89Zr-trastuzumab (\~37 MBq) will be injected. The HER2-PET will be performed 4 days after tracerinjection.

Also known as: HER2-PET, Injection of 89Zr-trastuzumab followed by PET scan

Molecular imaging

Eligibility Criteria

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

You may qualify if:

• Patient with first presentation of MBC, regardless of ER and HER2 status of the primary tumor, who is eligible for first-line systemic therapy.
• Patient with non-rapidly progressive MBC, not requiring urgent initiation of chemotherapy, based on clinician's evaluation which may include:
• no recent (\< 2 weeks prior to screening visit) significant worsening of MBC related signs and symptoms according to patient history.
• in case of liver metastases: no significant increase in liver function tests alanine aminotransferase aspartate transaminase (ASAT) and alanine transaminase (ALAT) in 2 weeks prior to screening visit. (Significant increase of liver function test is defined as 50% increase of absolute amount of ASAT/ALAT.)
• Patients in whom standard imaging work-up of MBC was recently (≤ 28 days) performed. Standard imaging must include: CT chest/abdomen, 18F-FDG-PET and bone scintigraphy.
• Patient with measurable or clinically evaluable (bone only) disease on recent standard work up of MBC are eligible.
• Metastatic lesion(s) of which a histological biopsy can safely be obtained according to standard clinical care procedures.
• Primary tumor blocks available for confirmatory central laboratory ER/HER2 testing in the UMCG. If available a snap frozen sample of the primary tumor will also be centralized in the University Medical Center Groningen (UMCG).
• WHO performance status 0-2.
• Patient is able to undergo PET imaging procedures.
• Age \>18 years of age, willing and able to comply with the protocol as judged by the investigator.
• Signed written informed consent.

You may not qualify if:

• Contraindications for systemic treatment (as will be assigned based on biopsy and experimental scan results), either chemotherapy, hormonal therapy or anti-HER2 therapy, based on clinical judgment of treating medical oncologist and patient history.
• Pregnant or lactating women.
• Prior allergic reaction to immunoglobulins or immunoglobulin allergy.
• Inability to comply with study procedures.
• Rapidly progressive (visceral) disease requiring rapid initiation of chemotherapy.

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Amsterdam UMC, location VUmc: collaborator
• University Medical Center Nijmegen: collaborator

Study Sites (3)

VU University Medical Center

Amsterdam, Netherlands

Location

University Medical Center

Groningen, 9700RB, Netherlands

Location

University Medical Center St. Radboud

Nijmegen, Netherlands

Location

Related Publications (2)

• Boers J, Eisses B, Zwager MC, van Geel JJL, Bensch F, de Vries EFJ, Hospers GAP, Glaudemans AWJM, Brouwers AH, den Dekker MAM, Elias SG, Kuip EJM, van Herpen CML, Jager A, van der Veldt AAM, Oprea-Lager DE, de Vries EGE, van der Vegt B, Menke-van der Houven van Oordt WC, Schroder CP; IMPACT-Metastatic Breast Consortium. Correlation between Histopathological Prognostic Tumor Characteristics and [18F]FDG Uptake in Corresponding Metastases in Newly Diagnosed Metastatic Breast Cancer. Diagnostics (Basel). 2024 Feb 14;14(4):416. doi: 10.3390/diagnostics14040416.

  PMID: 38396455 DERIVED

• van Geel JJL, Boers J, Elias SG, Glaudemans AWJM, de Vries EFJ, Hospers GAP, van Kruchten M, Kuip EJM, Jager A, Menke-van der Houven van Oordt WC, van der Vegt B, de Vries EGE, Schroder CP; IMPACT-Metastatic Breast Consortium. Clinical Validity of 16alpha-[18F]Fluoro-17beta-Estradiol Positron Emission Tomography/Computed Tomography to Assess Estrogen Receptor Status in Newly Diagnosed Metastatic Breast Cancer. J Clin Oncol. 2022 Nov 1;40(31):3642-3652. doi: 10.1200/JCO.22.00400. Epub 2022 May 18.

  PMID: 35584346 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Molecular Imaging; proto-oncogene protein c-fes-fps

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Molecular Probe Techniques; Investigative Techniques

Study Officials

• Carolien Schröder, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• Willemien Menke, MD, PhD

  VUMC

  PRINCIPAL INVESTIGATOR

• Winette vd Graaf, MD, PhD

  RUMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 3, 2013
• First Posted: October 8, 2013
• Study Start: August 30, 2013
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: November 20, 2024

Record last verified: 2024-11

Locations

NL (3)