Megestrol Acetate for Fatigue Management in T-DXd Treated Breast Cancer (MEGA-TACT-BC3)

A Multicenter, Double-Blind, Placebo-Controlled, Phase III Clinical Trial Evaluating Megestrol Acetate for the Management of Fatigue in Advanced Breast Cancer Patients Treatment With Trastuzumab Deruxtecan

This study aims to evaluate whether the combination of Megestrol Acetate at the initiation of Trastuzumab Deruxtecan (T-DXd) treatment can effectively prevent and alleviate T-DXd-related fatigue, thereby improving the quality of life for advanced breast cancer patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced/Metastatic Breast Cancer; HER2+, Low, or Ultralow Advanced/Metastatic Breast Cancer
• Intervention / Treatment: Drug: Megestrol Acetate + Trastuzumab Deruxtecan; Drug: Placebo + Trastuzumab Deruxtecan

Detailed Description

Evaluate the efficacy and safety of Megestrol Acetate (MA) in improving fatigue in breast cancer patients after T-DXd treatment.

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Meiting Chen Doctor, PhD / Doctorate; Phone Number: 02087341812; Email: chenmt@sysucc.org.cn

Study Locations

• China
  • Yuexiu District
    • Guangzhou, Yuexiu District, China, 510060
      • Sun Yat-Sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female, aged 18-75 years
2. Pathologically confirmed inoperable or metastatic breast cancer with complete ER, PR, and HER2 status
3. HER2-positive (IHC 3+ or IHC 2+ with FISH positive), HER2-low (IHC 1+ or IHC 2+ with FISH negative), or HER2-ultralow (IHC 0 with ≤10% weak incomplete membrane staining) [most recent specimen used]
4. Investigator-assessed indication for Trastuzumab Deruxtecan (T-DXd) therapy
5. No prior treatment with Trastuzumab Deruxtecan
6. Received ≤5 lines (including 5 lines) of prior chemotherapy
7. ECOG Performance Status 0-1
8. Estimated life expectancy ≥12 weeks
9. Adequate organ function
10. Reliable contraception or negative serum/urine pregnancy test within 7 days prior to enrollment; willing to use appropriate contraception during study and for 8 weeks after last dose
11. Voluntary participation with good compliance

Exclusion Criteria:

1. Severe underlying disease, comorbidities, active infection, or severe metabolic disorders
2. Clinically significant severe fatigue at baseline (FACIT-F score <30)
3. Currently receiving other antitumor therapies
4. Pregnant or lactating patients
5. Poor compliance or unable to complete normal follow-up
6. History of allergy to megestrol acetate or other components of the formulation
7. History of thromboembolism (use with caution)
8. Other malignancies diagnosed within 5 years, except: resected non-melanoma skin cancer, adequately treated cervical carcinoma in situ, locally radically treated prostate cancer, surgically radically treated ductal carcinoma in situ, or malignancies diagnosed >2 years ago with no current disease evidence and untreated for ≤2 years before randomization
9. Any condition judged by investigator that may affect study conduct or outcome assessment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group; Megestrol Acetate + Trastuzumab Deruxtecan	Drug: Megestrol Acetate + Trastuzumab Deruxtecan; Megestrol Acetate 160mg orally, days 1-5, every 3 weeks for 2 cycles; Combined with standard Trastuzumab Deruxtecan 5.4 mg/kg IV infusion every 3 weeks
Placebo Comparator: Control Group; Placebo + Trastuzumab Deruxtecan	Drug: Placebo + Trastuzumab Deruxtecan; Matched placebo 160mg orally, days 1-5, every 3 weeks for 2 cycles; Combined with standard Trastuzumab Deruxtecan 5.4 mg/kg IV infusion every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fatigue Score (FACIT-Fatigue Scale)	Measured by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Scale Version 4. Total score range: 0-52, with higher scores indicating less fatigue and better quality of life.	From baseline to end of 2nd cycle (approximately 6 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brief Fatigue Inventory (BFI) Score	The Brief Fatigue Inventory (BFI) is a self-reported instrument designed to assess the severity and impact of cancer-related fatigue. It consists of 9 items: 3 items assess fatigue severity at its "worst," "usual," and "current" states over the past 24 hours. 1）6 items assess the degree to which fatigue interferes with daily activities (general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life). 2）Scoring Criteria: Each item is rated on a 0 to 10 numerical scale, where 0 represents "no fatigue" or "does not interfere" and 10 represents "as bad as you can imagine" or "completely interferes." The total score is calculated as the average of the 9 items (range: 0-10). Mild fatigue: 1 to 3 Moderate fatigue: 4 to 6 Severe fatigue: 7 to 10 Higher scores indicate greater fatigue severity and functional impairment.	Time Frame：Baseline (Day 1 of Cycle 1), Day 7 of Cycle 1, Cycle 2 (Day 1), Day 8 of Cycle 2, and Cycle 3 (Day 1).（each cycle is 28 days）
Objective Response Rate (ORR)	Including Complete Response (CR) and Partial Response (PR) per RECIST 1.1 criteria	Assessed every 6 weeks up to 24 weeks
Patient Reported Outcomes (PRO)	EORTC QLQ-C30 is a 30-item questionnaire used to assess the quality of life of cancer patients. It includes: 5 Functional Scales: Physical, role, cognitive, emotional, and social functioning. 3 Symptom Scales: Fatigue, pain, and nausea/vomiting. A Global Health Status/Quality of Life (GHS/QoL) scale. 6 Single Items: Dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficultie EORTC QLQ-BR45 is a 45-item breast cancer-specific module used to assess quality of life. It consists of functional scales (e.g., body image, sexual functioning, breast satisfaction) and symptom scales (e.g., systemic therapy side effects, upset by hair loss, arm/breast symptoms, and skin/mucosal reactions to targeted therapies). Scores are linearly transformed to a range of 0 to 100. For functional scales, a higher score represents a higher level of functioning/better quality of life. For symptom scales, a higher score represents a greater symptom burden or more severe side effects	Baseline (Day 1 of Cycle 1), Day 7 of Cycle 1, Cycle 2 (Day 1), Day 8 of Cycle 2, and Cycle 3 (Day 1)（each cycle is 28 days）
Safety and Tolerability	1. Incidence of Adverse Events (AEs) graded by CTCAE v5.0	From first dose up to 30 days after last dose

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Jiajia Huang, PhD / Doctorate, Sun Yat-Sen University Cancer Center

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2031

Study Registration Dates

• First Submitted: April 9, 2026
• First Submitted That Met QC Criteria: April 15, 2026
• First Posted (Actual): April 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Megestrol Acetate; Megestrol Acetate + Trastuzumab Deruxtecan
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Megestrol; Megestrol Acetate; trastuzumab deruxtecan
• Other Study ID Numbers: MEGA-TACT-BC3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No