Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 3:43 PM
Ignite Modification Date:
2025-12-24 @ 3:43 PM
NCT ID:
NCT06837792
Brief Summary:
"This is a randomized phase II, two-arm, open label, clinical trial to identify LP-WGS ctDNA biomarker to predict T-DXd response in low-HER2 expressing advanced breast cancer patients compared with endocrine therapy. The hormone receptor (HR)-positive low-HER2 advanced breast cancer patients (HER2 IHC 1+ or 2+ \& ISH negative, n=141) who progressed on 1st line endocrine + CDK4/6 inhibitor therapy and received no other systemic therapy for advanced disease are enrolled in this study. Patients are 2:1 randomized to receive T-DXd (5.4mg/kg every 3 weeks, n=94) or endocrine therapy of physician's choice (TPC: fulvestrant, fulvestrant + alpelisib, Fulvestrant + Capivasertib, exemestane, exemestane + everolimus, or tamoxifen, n=47, fulvestrant + alpelisib can be selected in PIK3CA activating mutation positive patients, Fulvestrant + Capivasertib can be selected in 1 or More mutation positive of PIK3CA/AKT1/PTEN). The mandatory baseline archival tissue and ctDNA collection followed by on-treatment ctDNA collection (Cycle 1, Cycle 2, and Cycle 6) and ctDNA collection at progression will be performed in this study.
The primary endpoint is PFS after randomization in two treatment arms. The secondary endpoints include overall survival (OS), objective response rate (ORR), progression-free survival (PFS2), adverse events by CTCAE 5.0 criteria, and Quality of life (QoL) measured by EORTC-QLQ-C30 and EORTC-QLQ-BR23 evaluated by questionnaire. The exploratory endpoints are to identify ctDNA biomarkers to predict the TDxd treatment outcome (PFS, OS, ORR) compared to endocrine therapy in HER2-low advanced breast cancer patients and to assess the accordance of genomic profiles between ctDNA and tumor tissues. Predictive biomarkers include copy number aberration (CNA) of gene loci, total ctDNA CNA burden, mutations, ctDNA-based molecular subtype, or HER2 amplicon copy number on LP-WGS ctDNA analysis. The investigator believe this trial will identify crucial circulating biomarkers for T-DXd treatment response in low-HER2 patients, which can guide right patient selection and potential molecular target identification to maximize T-DXd response and to overcome T-DXd resistance.
Detailed Description:
Study Design: Randomized phase II, two-arm, randomized, open label study
\- The Hormone receptor (HR)-positive HER2-low advanced breast cancer patients (HER2 IHC 1+ or 2+ \& ISH negative, n=141) who progressed on first-line endocrine + CDK4/6 inhibitor therapy for advanced disease will be enrolled in this study. Patients will be 2:1 randomized to experimental and control treatment arms by stratification factors below
Stratification factor
1. Visceral metastasis (with visceral metastasis versus without visceral metastasis)
2. Progression-free survival on prior CDK4/6 inhibitor therapy (\< 6 months versus ≥ 6 months)
* In the experimental treatment arm (n=94), patients receive trastuzumab deruxtecan (T-Ddx) 5.4mg/kg intravenous infusion every 3 weeks. In the control treatment arm (n=47), patients receive endocrine therapy of physicians' choice (TPC: fulvestrant, fulvestrant + alpelisib, exemestane, exemestane + everolimus, or tamoxifen; fulvestrant + alpelisib can be selected in PIK3CA activating mutation positive patients). The study treatment will continue until disease progression by RECIST 1.1, unacceptable toxicity, end of study, or death.
* This study both enrolls pre- and post-menopausal patients, and pre-menopausal patients should receive ovarian function suppression treatment (GnRH agonist injection or surgical bilateral oophorectomy) while receiving fulvestrant or aromatase inhibitor treatment in the control arm.
* The endocrine TPC is pre-selected by investigator in screening period before randomization. The regimens that the patient received for advanced disease before cannot be selected. The regimen that the patients received for (neo)adjuvant therapy for breast cancer before cannot be selected unless the recurrence of disease was diagnosed \> 1 year after the completion of the (neo)adjuvant therapy.
* The evaluation of tumor response by computed tomography or magnetic resonance imaging of the chest, abdomen, and pelvis will be performed every 9 weeks from the date of randomization for 54 weeks and performed every 12 weeks after then until objective (RECIST 1.1 defined) disease progression.
* Mandatory baseline tissue and ctDNA collection followed by three on-treatment ctDNA samples (Day 1 of Cycle 2, Cycle 3, and Cycle 6) will be collected. The post-treatment ctDNA (mandatory) and tumor tissues (optional) will be also collected
* The patient samples will be evaluated to identify predictive biomarkers including copy number aberration (CNA), mutations, molecular subtype, or HRD status on LP-WGS ctDNA analysis.
Study:
NCT06837792
Study Brief:
Protocol Section:
NCT06837792