NCT01772472已完成3 期
A Randomized, Multicenter, Open-Label Phase III Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy for Patients With HER2-Positive Primary Breast Cancer Who Have Residual Tumor Present Pathologically in the Breast or Axillary Lymph Nodes Following Preoperative Therapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,486
- 试验地点
- 294
- 主要终点
- Invasive Disease-free Survival (IDFS) Rate at 3 Years
研究概览
简要总结
This 2-arm, randomized, open-label study will evaluate the efficacy and safety of trastuzumab emtansine versus trastuzumab as adjuvant therapy in patients with HER2-positive breast cancer who have residual tumor present in the breast or axillary lymph nodes following preoperative therapy. Eligible patients will be randomized to receive either trastuzumab emtansine 3.6 mg/kg or trastuzumab 6 mg/kg intravenously every 3 weeks for 14 cycles. Radiotherapy and/or hormone therapy will be given in addition if indicated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patient, >/= 18 years of age
- •HER2-positive breast cancer
- •Histologically confirmed invasive breast carcinoma
- •Clinical stage T1-4/N0-3/M0 at presentation (patients with T1a/bN0 tumors will not be eligible)
- •Completion of preoperative systemic chemotherapy and HER2-directed treatment consisting of at least 6 cycles of chemotherapy with a total duration of at least 16 weeks, including at least 9 weeks of trastuzumab and at least 9 weeks of taxane-based therapy
- •Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes as specified in protocol
- •Pathological evidence of residual invasive carcinoma in the breast or axillary lymph nodes following completion of preoperative therapy
- •An interval of no more than 12 weeks between the date of surgery and the date of randomization
- •Known hormone-receptor status
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Adequate hematologic, renal and liver function
- •Screening Left ventricular ejection fraction (LVEF) >/= 50% on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) after receiving neoadjuvant chemotherapy and no decrease in LVEF by more than 15% absolute points from the pre-chemotherapy LVEF. Or, if pre-chemotherapy LVEF was not assessed, the screening LVEF must be >/= 55% after completion of neoadjuvant chemotherapy.
- •For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose of study drug
- •Documentation of hepatitis B virus and hepatitis C virus serology is required
排除标准
- •Stage IV (metastatic) breast cancer
- •History of any prior (ipsi- or contralateral breast cancer except lobular carcinoma in situ
- •Evidence of clinically evident gross residual or recurrent disease following preoperative therapy and surgery
- •Progressive disease during preoperative systemic therapy
- •Treatment with any anti-cancer investigational drug within 28 days prior to commencing study treatment
- •History of other malignancy within the last 5 years except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other non-breast malignancies with a similar outcome to those mentioned above
- •Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons
- •Current NCI CTCAE (Version 4.0) Grade >/= 2 peripheral neuropathy
- •History of exposure to the following cumulative doses of anthracyclines: Doxorubicin > 240 mg/m2; Epirubicin or Liposomal Doxorubicin-Hydrochloride (Myocet®) > 480 mg/m2; For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m2
- •Cardiopulmonary dysfunction as defined by protocol
- •Prior treatment with trastuzumab emtansine
- •Current severe, uncontrolled systemic disease
- •Pregnant or lactating women
- •Any known active liver disease, e.g. due to HBV, HCV, autoimmune hepatic disorders, or sclerosing cholangitis
- •Concurrent serious uncontrolled infections requiring treatment or known infection with HIV
- •History of intolerance, including Grade 3 to 4 infusion reaction or hypersensitivity to trastuzumab or murine proteins or any components of the product
研究组 & 干预措施
Trastuzumab
Active Comparator
干预措施: trastuzumab (Drug)
Trastuzumab emtansine
Experimental
干预措施: trastuzumab emtansine (Drug)
结局指标
主要结局
Invasive Disease-free Survival (IDFS) Rate at 3 Years
时间窗: At Year 3
IDFS event was defined as the first occurrence of any one of the following events: ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site-other than the 2 above-mentioned sites - that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer); contralateral invasive breast cancer; death attributable to any cause including breast cancer, non-breast cancer or unknown cause . 3-year IDFS rate in ITT population was estimated using Kaplan Meier (KM) method and the percentage of participants who were event-free 3 years after randomization was estimated.
次要结局
- IDFS Including Second Primary Non-breast Cancer (SPNBC) Rate at 3 Years(At Year 3)
- IDFS Including SPNBC Rate at 7 Years(At Year 7)
- IDFS Including SPNBC Rate at 8 Years(At Year 8)
- Disease-free Survival (DFS) Rate at 3 Years(At Year 3)
- DFS Rate at 7 Years(At Year 7)
- DFS Rate at 8 Years(At Year 8)
- Overall Survival (OS) Rate at 5 Years(At Year 5)
- OS Rate at 7 Years(At Year 7)
- OS Rate at 8 Years(At Year 8)
- Distant Recurrence-free Interval (DRFI) Rate at 3 Years(At Year 3)
- DRFI Rate at 7 Years(At Year 7)
- DRFI Rate at 8 Years(At Year 8)
- Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From signing of informed consent till end of follow up (up to approximately 131 months))
- Percentage of Participants With Cardiac Events as Adjudicated by the Cardiac Review Committee(Up to approximately 126 months)
- Percentage of Participants With Hepatotoxicity Events as Adjudicated by the Hepatic Review Committee(Up to approximately 64 months)
- Number of Participants Who Discontinued Treatment Due to AEs(Up to approximately 9.6 months)
- Number of Participants With AEs and SAEs Leading to Death(From signing of informed consent till end of follow up (up to approximately 131 months))
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30)(Baseline, Cycles 5 &11, Follow-up (FU) Month 6, FU Month 12 (1 cycle = 21 days))
- Change From Baseline in EORTC Quality of Life Questionnaire - Breast Cancer (QLQ-BR23)(Baseline, Cycles 5 &11, Follow-up (FU) Month 6, FU Month 12 (1 cycle = 21 days))
- Serum Concentrations of Trastuzumab Emtansine(Pre-infusion on Cycles 1, 2, 4 and 5; 15-30 minutes and 2 hours post-infusion on Cycles 1 and 4; treatment discontinuation/completion visit (up to approximately 64 months) (1 cycle = 21 days))
- Plasma Concentrations of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1)(Pre-infusion, 15-30 minutes and 2 hour post-infusion on Cycles 1 and 4 (1 cycle = 21 days))
- Serum Concentrations of Trastuzumab(Pre-infusion and 15-30 minutes post-infusion on Cycles 1 and 4; Treatment completion/discontinuation visit (up to approximately 64 months) (1 cycle = 21 days))
- Serum Concentrations of Total Trastuzumab(Pre-infusion on Day 1 of Cycles 1, 2, 4, and 5; 15-30 minutes and 2 hours post-infusion on Day 1 of Cycles 1 and 4 (1 cycle = 21 days))
- Median Duration of Trastuzumab Emtansine Exposure(Up to 12 months)
- Number of Participants With Positive Anti-drug Antibodies (ADAs) to Trastuzumab Emtansine(Baseline (Day1 of Cycle1) and Post Baseline (Day 1 of Cycle 4 up to 3-4 months after last dose of the drug [up to approximately 13.6 months]))
- Number of Participants With Positive ADAs to Trastuzumab(Baseline (Day1 of Cycle1) and Post Baseline (Day 1 of Cycle 4 up to 3-4 months after last dose of the drug [up to approximately 13.6 months]))
研究者
研究点 (294)
Loading locations...
相似试验
已完成
2 期
A Study of Trastuzumab Emtansine (T-DM1) Sequentially With Anthracycline-based Chemotherapy, as Adjuvant or Neoadjuvant Therapy for Patients With Early Stage Herceptin (HER)2-positive Breast CancerBreast CancerNCT01196052Hoffmann-La Roche153
已完成
3 期
A Phase III Trial of Pertuzumab Retreatment in Previously Pertuzumab Treated Her2-Positive Advanced Breast CancerHER2-positive Locally Advanced or Metastatic Breast CancerNCT02514681Japan Breast Cancer Research Group226
已完成
3 期
A Two-Arm Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Chinese Participants With HER2-Positive Early Breast CancerHER2-positive Early Breast CancerNCT04024462Hoffmann-La Roche200
进行中（未招募）
2 期
Stage I HER2 Positive Invasive Breast Cancer De-escalation Study(IRIS)Breast CancerNCT04383275Fudan University367
已完成
3 期
A Study of Trastuzumab Emtansine (Kadcyla) Plus Pertuzumab (Perjeta) Following Anthracyclines in Comparison With Trastuzumab (Herceptin) Plus Pertuzumab and a Taxane Following Anthracyclines as Adjuvant Therapy in Participants With Operable HER2-Positive Primary Breast CancerBreast CancerNCT01966471Hoffmann-La Roche1,846
相关资讯
Kadcyla Shows Sustained Survival Benefit in HER2-Positive Early Breast Cancer• Long-term analysis of the KATHERINE trial reveals that Kadcyla (T-DM1) significantly improves overall survival in HER2-positive early breast cancer patients with residual invasive disease.
• The study demonstrated a 7-year overall survival rate of 89.1% with T-DM1 compared to 84.4% with trastuzumab monotherapy, indicating a substantial survival advantage.
• Kadcyla also showed a sustained improvement in invasive disease-free survival, with a 7-year rate of 80.8% versus 67.1% for trastuzumab, reinforcing its efficacy.
• The safety profile of T-DM1 was acceptable, with manageable adverse events, further supporting its use in the adjuvant treatment of high-risk early breast cancer.last yearHER2-Targeted Therapies Solidify Role in Early-Stage HER2-Positive Breast Cancer Treatment• Neoadjuvant HER2-targeted therapy, including trastuzumab and pertuzumab, has become a standard of care for stage II/III HER2-positive breast cancer, improving event-free and overall survival.
• The NeoSphere trial established pathologic complete response (pCR) as a primary endpoint for neoadjuvant drug approval, demonstrating the efficacy of docetaxel, trastuzumab, and pertuzumab.
• The KATHERINE trial demonstrated that ado-trastuzumab emtansine (T-DM1) improves disease-free and overall survival in patients with residual invasive disease after neoadjuvant HER2-targeted therapy.
• Subcutaneous trastuzumab and pertuzumab offer similar efficacy to IV formulations, with patient preference leaning towards the subcutaneous option due to convenience.last year