A Phase II Study of Flat-Dose Trastuzumab Deruxtecan (T-DXd) in Endocrine Refractory HER2-low advanced unresectable/metastatic Breast Cancer (FaiTH-Low)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- ICMR
- 入组人数
- 32
- 试验地点
- 1
研究概览
简要总结
Study Title: A Phase II Study of Flat-Dose Trastuzumab Deruxtecan in Endocrine Refractory HER2 Low Advanced Unresectable/Metastatic Breast Cancer FaiTH Low.Introduction: Breast cancer is one of the most common cancers worldwide. HER2 low advanced or metastatic breast cancer patients have a poorer prognosis after becoming endocrine resistant. Trastuzumab Deruxtecan , an antibody-drug conjugate , has shown promising efficacy in treating HER2-low cancers. This study explores the effectiveness of a flat 100 mg dose compared to the historical standard 5.4 mg per kg dose. Hypothesis: A flat 100 mg dose of TDXd can provide similar efficacy to the standard weight-based dose while improving safety, reducing costs, and enhancing accessibility for patients. Study Objectives:Primary Objective: Evaluate Progression Free Survival with a flat 100 mg dose of TDXdSecondary Objectives: Assess overall response rate , disease control rate, and overall survivalAdverse Event Incidence and Severity with graded according to CTCAE v 5.0. Quality of Life : Assessments with EORTC QLQ C30 Study Design Type: Single-arm Simon Phase II trial. Participants: HER2 low, ER positive endocrine refractory metastatic breast cancer patients post 1 line of chemotherapy. Duration: 24 months of accrual and 12 months of follow up. Sample Size: 32 patients 11 in Stage I expansion to 21 if efficacy is observed.Dosing: Flat-dose 100 mg IV infusion every 3 weeks. Eligibility Criteria Inclusion Criteria: Patients more than18 years with unresectable or metastatic ER positive and HER2 low with IHC 1 positive or IHC 2 positive or ISH Non-amplified breast cancer.Refractory to endocrine therapy. Prior treatment with 1 to 2 chemotherapy lines in the metastatic setting. No prior anti HER2 therapy. ECOG performance status 0 to 1. Exclusion Criteria: Patients with triple-negative breast cancer TNBC will be excluded. Severe heart disease, recent myocardial infarction, or symptomatic heart failure. Interstitial lung disease or significant pulmonary conditions. Active CNS metastases requiring steroids. Data Management and Statistical Plan Kaplan Meier curves will analyze survival outcomes. Descriptive statistics for toxicity and response rates. Intent-to-treat analysis will be conducted. Anticipated Risks: Potential side effects include neutropenia, nausea, ILD, fatigue, and cardiac toxicity. Benefits: Potential comparable efficacy at a lower dose with fewer toxicities and cost reductions, making treatment more accessible.Ethical Considerations and Patient Confidentiality Conducted per ICMR guidelines and the Declaration of Helsinki. Informed consent is required.Confidentiality was maintained with de identified data storage. This trial aims to establish a cost effective, safer alternative to standard dose TDXd for HER2 low breast cancer patients while maintaining treatment efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •Patients (above 18 years age) with unresectable/metastatic ER-positive and HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer.
- •Refractory to endocrine therapy.
- •Prior treatment with 1–2 chemotherapy lines in the metastatic setting.
- •No prior anti-HER2 therapy.
- •ECOG performance status 0–1.
排除标准
- •Patients with triple-negative breast cancer (TNBC) will be excluded.
- •Has a medical history of myocardial infarction within 6 months before enrollment.
- •Has a history of symptomatic congestive heart failure.
- •Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
- •Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
- •However, subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy.
- •A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.
研究者
Prabhat Bhargava
Tata Memorial Centre