HER2-PET Imaging in HER2-low Breast Cancers

NCT06732336 | Recruiting Phase 1

• 1 other identifier: 2025-5574
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

A strategy to target the oncogenic receptor HER2 using a version of the anti-HER2 therapeutic antibody trastuzumab coupled to desferrioxamine (DFO) and radiolabeled with zirconium-89 (\[89Zr\]-DFO-trastuzumab) has been successfully evaluated in our group in preclinical settings. Clinical studies by other groups in recent years have shown the potential of targeting HER2+ lesions with \[89Zr\]-DFO-trastuzumab in patients with HER2+ cancers. We now want to establish the diagnostic potential of a protocol adding \[89Zr\]-DFO-trastuzumab PET imaging to FDG PET already used in the clinic for the detection of HER2-expressing cancers, including low expression levels considered until now as HER2-negative (HER2-low, IHC score 1+ and 2+ without FISH amplification of the HER2 locus). The HER2-low status has recently gained relevance thanks to large studies showing the efficacy of immunotherapy combined with drugs such as Enhertu (trastuzumab-deruxtecan), while trastuzumab alone was traditionally only effective for HER2+ cancers (IHC score 2+/FISH+, or 3+). In particular, we aim to develop a method to assess whole-body intertumoral heterogeneity in HER2 expression in order to detect cases with heterogeneous diseases and thus better stage patients and guide the optimal choice of personalized and targeted treatment to use. More specifically, the project aims to image with \[89Zr\]-DFO-trastuzumab PET patients with cancer, particularly breast cancer, but also esophageal, gastric, ovarian, endometrial and lung cancer, and whose primary tumor status is HER2-low.

Conditions

Breast Cancer Metastatic

Keywords

HER2; HER2-low; PET; Breast cancer; 89Zr-trastuzumab

Outcome Measures

Primary Outcomes (1)

• Evaluate 89Zr-trastuzumab PET imaging in a HER2-low breast cancer patient cohort

  Patients (n=40) will be injected with a dose of 89Zr-trastuzumab, then imaged by PET/CT 3-6 days later. Images will be analysed, and each suspect foci will have a region-of-interest (ROI) drawn on it. 89Zr-trastuzumab uptake in suspected tumors will be measured as a standard uptake value (SUV). SUVs will be compared with the pathological status and grade from the primary tumor and/or distant biopsied lesions (when available).

  18 months

Study Arms (1)

89Zr-trastuzumab PET/CT imaging of HER2-low patients

EXPERIMENTAL

Following their inform consent, HER2-low breast cancer patients will be invited to come to our research center twice. The first time patients will receive an intravenous dose of 10-50mg trastuzumab, followed by a 0.5 MBq/kg (max 60 MBq) dose of 89Zr-trastuzumab. Patients will come back for a second visit 3-6 days later to get their PET/CT imaging examination. Images will be evaluated by two PET-trained physicians, and analysed by an imaging scientist.

Diagnostic Test: 89Zr-trastuzumab

Interventions

89Zr-trastuzumab DIAGNOSTIC_TEST

Patients will receive an intravenous dose of 0.5 MBq/kg (max 60 MBq) of 89Zr-trastuzumab in order to perform a PET imaging session 3-6 days later.

89Zr-trastuzumab PET/CT imaging of HER2-low patients

Eligibility Criteria

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

You may qualify if:

• HER2-low metastatic breast cancer;
• At least 18 years-old ;
• Able to stay in supine position for at least 30 minutes;
• Written inform consent.

You may not qualify if:

• Pregnancy or concomitant breast feeding;
• Hepatic disorders such as cirrhosis, hepatitis, or any other liver condition judged as significant by the treating physician and that could impair the biliary excretion of 89Zr-trastuzumab;
• Renal disorders considered significant by the treating physician and that could impair the normal elimination of 89Zr-trastuzumab;
• Known hypersensitivity or allergy to trastuzumab, desferrioxamine, or any constituents of 89Zr-trastuzumab.

Sponsors & Collaborators

• Centre de recherche du Centre hospitalier universitaire de Sherbrooke: lead
• Université de Sherbrooke: collaborator

Study Sites (1)

Centre de recherche du CHUS

Sherbrooke, Quebec, J1H5N4, Canada

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Éric E Turcotte, MD, FRCPC

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michel Paquette, PhD

CONTACT

819-346-1110; michel.paquette@usherbrooke.ca

Esteban Espinosa-Bentancourt

CONTACT

819-346-1110; Esteban.Espinosa-Bentancourt@USherbrooke.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 89Zr-trastuzumab PET imaging of HER2-low breast cancer patients

Study Record Dates

• First Submitted: December 9, 2024
• First Posted: December 13, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)