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NCT Number: NCT07130344

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

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.

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Key information

Conditions

Metastatic Breast Cancer Breast Diseases Breast Neoplasms HER 2 Low-expressing Breast Cancer Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

Screening period will last 28 days. Each participant will have baseline evaluation by TAP CT-scan, bone scintigraphy and 18F-FDG PET-CT.

After randomization, patient will start T-DXd treatment according to SOC until progression or toxicity. Patient will be followed by TAP CT-scan and bone scintigraphy (SOC arm) or 18F-FDG PET-CT (experimental arm) every 3 months, until progression or new treatment initiation or death or until 2 years whichever occurs first.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age greater than or equal to 18 years at inclusion
  • 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
  • Signed informed consent obtained before inclusion (after giving clear, fair and appropriate information)

Exclusion criteria

  • 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

Treatment and study plan

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.

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.

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.

Primary outcomes

  1. Objective response rate

    Time frame: at 3 months

    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.

Secondary outcomes

  1. Progression-free survival

    Time frame: 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.

    Progression events will be collected (progression according to PERCIST 1.0 criteria in experimental arm and RECIST 1.1 criteria in SOC arm or death whatever the cause).

  2. Time until new therapy initiation

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

    Time from inclusion to initiation of new therapy.

  3. Overall survival

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

    The patient's condition (alive, deceased from whatever cause or lost to follow-up) will be collected. Patients alive at the time of analysis will be censored on the date of last contact.

  4. Response duration

    Time frame: 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 from date of first documented response (complete or partial response) to date of first subsequent progression or death from any cause.

  5. Patient Quality of life

    Time frame: 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.

    Assessment of all dimensions of the European Organization for Research and Treatment of Cancer (EORTC) QLG Core Questionnaire (EORTC QLQ-C30). Difference on specific symptom scales (from 1 = " not at all " to 4 = " very much ", or from 1 = " really bad " to 7 = " excellent ").

Study contacts

Contact information is provided by the study sponsor or research team.

Anne ANTHONY

CONTACT

[email protected]

36876252413 ext. 33

Valérie SARTORI

CONTACT

[email protected]

368767223 ext. 33

Sponsors and collaborators

Lead sponsor

Centre Paul Strauss

Other

Registry information

Acronym: PERPETUAL

Important dates

Study start
2025
Primary completion
2028
Study completion
2030
First posted
Aug 19, 2025
Registry last updated
Sep 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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