Disease Extent in Stage IV Lobular Carcinoma: the Aid of Imaging and Liquid Biopsy Analyses

N/ANot Yet RecruitingNCT07635654

KU Leuven43 enrolled

Overview

Metastatic invasive lobular carcinoma (ILC) is a distinct breast cancer subtype characterized by loss of E-cadherin and a diffuse growth pattern that makes metastases difficult to detect with standard imaging such as computed tomography (CT) or 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET)/CT. As a result, disease burden in patients with ILC is frequently underestimated, progression is identified later than clinically optimal, and many patients are excluded from clinical trials due to insufficiently measurable disease. Whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) is a radiation-free imaging technique that has demonstrated improved sensitivity for detecting metastases-including peritoneal, bone, and nodal disease-in ILC. Retrospective studies suggest that WB-DWI/MRI can identify clinically relevant progression not visible on standard imaging. However, prospective evidence in ILC is lacking. Circulating tumor DNA (ctDNA) has also shown promise as a minimally invasive biomarker for monitoring treatment response, with early molecular changes often preceding radiologic progression, but data specific to ILC remain limited. The DELILA study is a prospective, multicenter clinical trial conducted at University Hospitals Leuven and Institut Jules Bordet. The study aims to enroll 43 patients starting first-line systemic therapy for metastatic hormone receptor positive human epidermal growth factor receptor 2 negative (HR+/HER2-) ILC. Participants undergo serial dual imaging-WB-DWI/MRI and standard-of-care imaging-at baseline, at 1 month, and approximately every 3 months for up to 30 months or until disease progression. At each imaging time point, blood samples are collected for ctDNA analysis and Ca15.3 tumor marker assessment. Patient-reported psychological burden related to repeated imaging and blood sampling is evaluated using validated questionnaires. The primary objective is to assess the added value of WB-DWI/MRI in detecting disease progression that informs clinical decision-making compared to standard imaging. Secondary objectives include evaluating whether ctDNA or Ca15.3 dynamics reflect disease evolution, assessing measurability of lesions with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and MRI-specific criteria, identifying early biomarkers of treatment response using Apparent Diffusion Coefficient (ADC) changes and ctDNA kinetics, and characterizing the psychological impact of trial procedures. This study will provide the first adequately powered prospective evidence on the clinical utility of WB-DWI/MRI and liquid biopsy monitoring in metastatic ILC. Results may support implementation of WB-DWI/MRI as a routine imaging strategy, guide imaging frequency through biomarker-informed approaches, and improve patient experience and trial eligibility for individuals living with metastatic ILC.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures 2. At least 18 years of age at the time of signing the Informed Consent Form (ICF) 3. ECOG from 0 to 2 4. Patient with stage IV ILC, either de novo or after prior (curative) treatment for early ILC. Histological subtype confirmed on primary tumor or on metastatic tissue. Patients that are diagnosed with stage IV breast cancer that have a mixed ILC/IBC-NST histology of the primary tumor (mixed histology within the same primary lesion) will also be able to participate and will be analyzed in an exploratory cohort. 5. Confirmation of hormone receptor positive (HR+)/HER2- disease either on new biopsy or archival tissue (e.g. primary tumor) 6. Multifocal or bilateral disease is allowed if all evaluated foci present with HR+/HER2- ILC 7. Starting first line of treatment for metastatic ILC Exclusion Criteria: 1. Presence of a contraindication to perform WB-DWI/MRI 2. Presence of severe claustrophobia 3. Presence of a contraindication to use IV contrast for CT or PET/CT (e.g. allergy, severe renal failure) in case a non-contrast PET/CT cannot be performed 4. Patients considered to have oligometastatic disease who are expected to undergo locoregional treatment 5. Presence of other malignancies in recent medical history (\<5 years) 6. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive 7. Adults who are the subject of a legal protection measure or who are unable to express their consent.

Outcomes

Primary Outcomes

Percentage of cases where WB-DWI/MRI contributed solely to the decision of progression and/or treatment change assessed by questionnaires filled out by the treating oncologist at the time of progression

Time frame: At the time of progression

Secondary Outcomes

ctDNA dynamics

ctDNA levels will be assessed at baseline and every 3 months. Changes in levels will be correlated with findings on imaging.

Time frame: At baseline, after 1 month of treatment, and every 3 months of treatment until disease progression or a maximum follow-up of 30 months (end of trial).

Measurability according to RECISTv1.1 criteria

Time frame: At baseline and every 3 months of treatment until disease progression or a maximum follow-up of 30 months (end of trial).

Measurability according to MRI-specific criteria

Measurability will be assessed on MRI by use of RECIST v1.1 criteria and RECISTv1.1 extended with MRI-specific criteria (similar to MY-RADS and MET-RADS-P).

Time frame: At baseline and every 3 months of treatment until disease progression or a maximum follow-up of 30 months (end of trial).

Disease extent on WB-DWI/MRI compared to SOC imaging

Disease extent on whole-body DWI/MRI (WB-DWI/MRI) is analyzed and compared with standard-of-care (SOC) imaging (e.g., CT, PET/CT, bone scan) using a combination of lesion detection, segmentation, and quantitative scoring methods. First, all visible lesions are identified on WB-DWI/MRI and SOC images using predefined anatomical regions. Lesions are counted and, where feasible, segmented to estimate tumor burden (e.g., total tumor volume).

Time frame: At baseline and every 3 months of treatment until disease progression or a maximum follow-up of 30 months (end of trial).

Lesion-level ADC dynamics

Quantitative assessment using ADC measurements will be incorporated to support treatment response evaluation. Diffusion-weighted images acquired at baseline and early follow-up are used to generate ADC maps; the lesion is segmented, and quantitative metrics (e.g., mean or percentile ADC) are extracted. The change in ADC (absolute or percentage) is then calculated, with a significant increase typically indicating response, while stable or decreased ADC suggests resistance.

Time frame: At baseline and after 1 month of treatment

Scores of psychological assessment questionnaires compared to baseline

Anxiety related to the imaging modalities will be assessed using the STAI-6 and Likert-10 scales, including evaluation of potential stressors associated with each imaging technique. The EORTC QLQ-COMU26 questionnaire will be used to assess patients' perceptions of imaging-related communication.

Time frame: At baseline, after 1 month of treatment, and every 3 months of treatment until disease progression or a maximum follow-up of 30 months (end of trial).

Scores of psychological assessment questionnaires compared between imaging modalities

Time frame: At baseline and every 3 months of treatment until disease progression or a maximum follow-up of 30 months (end of trial).

Disease Extent in Stage IV Lobular Carcinoma: the Aid of Imaging and Liquid Biopsy Analyses

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes