Advanced/Metastatic Breast Cancer, HER2+, Low, or Ultralow Advanced/Metastatic Breast Cancer
Conditions
Keywords
Megestrol Acetate, Megestrol Acetate + Trastuzumab Deruxtecan
Brief summary
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.
Detailed description
Evaluate the efficacy and safety of Megestrol Acetate (MA) in improving fatigue in breast cancer patients after T-DXd treatment.
Interventions
DRUGMegestrol 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
DRUGPlacebo + 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
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Intervention model description
T-DXd: 5.4 mg/kg, IV drip, q3w. MA/Placebo: 160 mg, PO, d1-5, q3w for 2 cycles
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fatigue Score (FACIT-Fatigue Scale) | From baseline to end of 2nd cycle (approximately 6 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Brief Fatigue Inventory (BFI) Score | 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） | 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. |
| Objective Response Rate (ORR) | Assessed every 6 weeks up to 24 weeks | Including Complete Response (CR) and Partial Response (PR) per RECIST 1.1 criteria |
| Patient Reported Outcomes (PRO) | 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） | 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 |
| Safety and Tolerability | From first dose up to 30 days after last dose | 1\. Incidence of Adverse Events (AEs) graded by CTCAE v5.0 |
Countries
China
Contacts
CONTACTMeiting Chen Doctor, PhD / Doctorate
PRINCIPAL_INVESTIGATORJiajia Huang, PhD / Doctorate
Sun Yat-Sen University Cancer Center
Outcome results
None listed