PERCIST Evaluation of Trastuzumab Deruxtecan in the Treatment of HER2 Low Breast Cancer

NCT07130344 | Not Yet Recruiting

• 1 other identifier: 2024-008
• Study Type: interventional
• Target: 262
• Locations: 1 country
• Sites: 1

Brief Summary

The development of trastuzumab deruxtecan (T-DXd), an anti-HER2 conjugated antibody, has changed the therapeutic landscape of breast cancer. Anti-HER2 molecules were previously used exclusively in cases of HER2-positive breast cancer (IHC HER2 3+ or HER2 2+ with amplified FISH/SISH). Since a couple of years, T-DXd is becoming a reference treatment in patients with low HER2 breast cancer (IHC 1+ or 2+ with non-amplified FISH/SISH) after hormone therapy and at least one line of chemotherapy. The results of the DB04 trial revealed that T-DXd increased progression-free survival and overall survival compared to investigator's choice chemotherapy, in HER2 low breast cancers patients after one or two previous lines of chemotherapy (Modi, S. et al., 2022). In several trials, T-DXd validation was done thanks to radiological evaluation based on conventional imaging, computed tomography scan (CT-scan) with or without contrast dye injection and bone scintigraphy. 18F-Fluorodeoxyglucose positron emission tomography coupled with computed tomography (18F-FDG PET-CT) represents a major tool for diagnosis, staging, and therapeutic follow-up in oncology. It was demonstrated that 18F-FDG PET-CT is more sensitive in detecting metastatic disease progression in HER2-positive breast cancer patients treated with trastuzumab and pertuzumab or trastuzumab and lapatinib (Ma, G. et al., 2023 et Lin, N. U. et al., 2015). Moreover, a prospective study investigated the correlation between the response rate defined by 18F-FDG PET-CT and thoraco-abdomino-pelvic CT-scan (TAP CT-scan) and the progression-free survival of patients with breast cancer. PET evaluation allowed better identification of responders versus non-responders, with a significant correlation with progression-free survival (Vogsen, M. et al., 2023). With this study, the investigators aim to determine the role of 18F-FDG PET-CT in evaluating T-DXd treatment in patients with metastatic low HER2 breast cancer. 18F-FDG PET-CT could be an earlier evaluation tool than CT-scan in identifying non-responsive patients; and thus, avoid continuing an expensive treatment with an unfavorable toxicity profile, which could worsen both patient prognosis and quality of life.

Conditions

Metastatic Breast Cancer; HER 2 Low-expressing Breast Cancer

Keywords

Breast Cancer; 18F-FDG PET-CT; T-DXd

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Radiological response according to PERCIST 1.0 criteria in experimental arm and RECIST 1.1 criteria in SOC arm. Number of patients who had an objective response at 3 months in both arms. The evaluation is carried out by the investigator.

  at 3 months

Secondary Outcomes (5)

• Progression-free survival

  Every 3 months until the date of first documented progression or new therapy initiation or date of death or until 2 years, whichever occurs first.

• Time until new therapy initiation

  Until initiation of a new therapy or until 2 years, whichever occurs first.

• Overall survival

  From date of inclusion until the date of death or lost to follow-up or until 2 years, whichever occurs first.

• Response duration

  Every 3 months until the date of first documented progression or new therapy initiation or date of death or until 2 years, whichever occurs first.

• Patient Quality of life

  Every 3 months until the date of first documented progression or new therapy initiation or date of death or until 2 years, whichever occurs first.

Study Arms (2)

SOC arm

ACTIVE COMPARATOR

Patient will be followed by TAP CT-scan and bone scintigraphy every 3 months, until progression or new treatment initiation or until 2 years whichever occurs first.

Procedure: TAP CT-scan; Procedure: Bone scintigraphy

Experimental arm

EXPERIMENTAL

Patient will be followed by 18F-FDG PET-CT every 3 months, until progression or new treatment initiation or until 2 years whichever occurs first.

Procedure: 18F-FDG PET-CT

Interventions

TAP CT-scan PROCEDURE

Patient in the SOC arm will be followed by TAP CT-scan every 3 months, until progression or new treatment initiation or until 2 years whichever occurs first.

SOC arm

Bone scintigraphy PROCEDURE

Patient in the SOC arm will be followed by bone scintigraphy every 3 months, until progression or new treatment initiation or until 2 years whichever occurs first.

SOC arm

18F-FDG PET-CT PROCEDURE

Patient in the experimental arm will be followed by 18F-FDG PET-CT every 3 months, until progression or new treatment initiation or until 2 years whichever occurs first.

Experimental arm

Eligibility Criteria

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

You may qualify if:

• Cytological or histological confirmation of the diagnosis of low HER2 breast cancer (IHC 1+ or 2+ with non-amplified FISH/SIS)
• Metastatic disease according to RECIST 1.1
• Indication of T-DXd treatment
• Patient (male or female of childbearing potential) using a highly effective contraceptive method
• Women of childbearing potential must have a negative pregnancy test within 72 hours before starting treatment
• Willingness and ability to comply with the visit schedule, treatment regimens, examinations and other procedures planned in the study
• Patient enrolled in a health insurance plan or beneficiary of such a plan

You may not qualify if:

• Allergy to contrast dye
• Contra-indication to PET-CT
• Any active infection or uncontrolled intercurrent pathology
• Patient with a life expectancy lower than 3 months
• Ongoing participation in another clinical trial with an investigational treatment
• Pregnant or breastfeeding women
• Persons deprived of their freedom or under guardianship or incapable of giving consent
• Any psychiatric illness/social situation that may limit compliance with study procedures or prevent the patient from giving written informed consent

Sponsors & Collaborators

• Centre Paul Strauss: lead

Study Sites (1)

ICANS

Strasbourg, 67033, France

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• François SOMME

  Institut de cancérologie Strasbourg Europe

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Valérie SARTORI

CONTACT

368767223; v.sartori@icans.eu

Anne ANTHONY

CONTACT

36876252413; an.anthony@icans.eu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2025
• First Posted: August 19, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): September 1, 2030
• Last Updated: September 10, 2025

Record last verified: 2025-09

Locations

FR (1)