NCT03811418撤回3 期
Phase III Study to Compare Trastuzumab-biosimilar (Kanjinti®) Plus Pertuzumab Plus Vinorelbine With Trastuzumab-biosimilar (Kanjinti®) Plus Pertuzumab Plus Docetaxel as First-line Treatment for HER2-positive Advanced Breast Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- iOMEDICO AG
- 试验地点
- 1
- 主要终点
- Patient-reported health-related quality of life (QoL): FACT-B
研究概览
简要总结
This is a randomized, open-label, two-arm, phase III trial in Germany to investigate whether vinorelbine-based triple combination presents a less toxic treatment option than docetaxel-based triple combination in patients with HER2-positive advanced breast cancer who have not previously received any systemic treatment in the metastatic setting.
The primary objective of the study is to compare patient-reported quality of life in the two treatment arms. Patients will be followed-up for survival until death or end of study after at least 79 deaths occured in each arm, whatever comes first.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed and dated written informed consent prior to beginning of protocol-specific procedures.
- •Histologically or cytologically confirmed adenocarcinoma of the breast. Locally advanced and inoperable or metastatic disease.
- •HER2-positive disease, defined as IHC status HER2+++ or CISH/FISH status positive.
- •Female patients aged ≥ 18 years.
- •In case of adjuvant treatment, disease-free interval of at least 12 months after completion of adjuvant treatment (excluding hormonal therapy).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
- •For women with childbearing potential, defined as physiologically capable of becoming pregnant:
- •Negative pregnancy test.
- •Agreement to use an effective form of contraception during study treatment and for 7 months after the last dose of study treatment.
- •Life expectancy of at least 12 weeks.
- •Adequate organ and bone marrow function
- •Fluent in spoken and written German and willing to answer the questionnaires
排除标准
- •Previous systemic treatment in palliative intention (chemotherapy, hormonal therapy and / or biological therapy)
- •Persistent peripheral sensory or motor neuropathy grade 2 or higher (NCI CTCAE v5.0)
- •Evidence of central nervous system metastases. CT or MRI of the brain is only mandatory in case of clinical suspicion of brain metastases
- •Current uncontrolled hypertension (systolic > 150 mmHg and / or diastolic > 100 mmHg) or clinically significant cardiovascular disease
- •History of LVEF < 50% during or after prior (neo)adjuvant therapy with trastuzumab
- •Current severe, uncontrolled systemic disease (e.g. cardiovascular, pulmonary, or metabolic disease, wound healing disorder, ulcers, or bone fractures, or severe fungal, bacterial or viral infection)
- •Major surgery within 28 days prior to start of study medication, or anticipation of the need for major surgery during the course of study treatment
- •Current known infection with HIV, HBV, or HCV (testing not required)
- •Dyspnea at rest due to complications of advanced malignancy, or other diseases requiring continuous oxygen therapy.
- •Known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies.
- •Participation in investigational studies within 30 days or five half-lives of the respective IMP, whichever is longer, prior randomization.
- •Pregnant or lactating women.
研究组 & 干预措施
Kanjinti/Pertuzumab plus Vinorelbine
Experimental
Patients will receive Kanjinti® (trastuzumab-biosimilar) plus pertuzumab plus vinorelbine.
干预措施: Trastuzumab (Drug)
Kanjinti/Pertuzumab plus Vinorelbine
Experimental
Patients will receive Kanjinti® (trastuzumab-biosimilar) plus pertuzumab plus vinorelbine.
干预措施: Pertuzumab (Drug)
Kanjinti/Pertuzumab plus Vinorelbine
Experimental
Patients will receive Kanjinti® (trastuzumab-biosimilar) plus pertuzumab plus vinorelbine.
干预措施: Vinorelbine (Drug)
Kanjinti/Pertuzumab plus Docetaxel
Active Comparator
Patients will receive Kanjinti® (trastuzumab-biosimilar) plus pertuzumab plus docetaxel.
干预措施: Trastuzumab (Drug)
Kanjinti/Pertuzumab plus Docetaxel
Active Comparator
Patients will receive Kanjinti® (trastuzumab-biosimilar) plus pertuzumab plus docetaxel.
干预措施: Pertuzumab (Drug)
Kanjinti/Pertuzumab plus Docetaxel
Active Comparator
Patients will receive Kanjinti® (trastuzumab-biosimilar) plus pertuzumab plus docetaxel.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Patient-reported health-related quality of life (QoL): FACT-B
时间窗: Baseline to week 18
Area under the curve (AUC) in the Functional Assessment of Cancer Therapy - Breast (FACT-B) questionnaire subscale Trial Outcome Index-Physical/Functional/Breast (TOI-PFB) after 18 weeks (irrespective of disease or treatment situation at that time point). Higher AUC indicates better quality of life. To calculate the TOI-PFB the three subscales Physical well-being (PWB - 7 statements), Functional well-being (FWB - 7 statements) and breast cancer subscale (BCS - 10 statements) are summed up. In all subscales each statement will be rated by the patient from 0 (not at all) - 4 (very much). Therefore ranges of subscales are: PWB 0 - 28; FWB 0 - 28; BCS 0 - 40; TOI-PFB 0 - 96; higher values indicate better quality of life.
次要结局
- Time to treatment failure (TTF)(Baseline, every 12 weeks after randomization (maximum up to 56 months))
- Patient-reported health-related quality of life (QoL): FACT-B TOI-PFB(Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).)
- Patient-reported health-related quality of life (QoL): FACT-B subscale social/family well-being (SWB)(Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).)
- Exploratory endpoint: Treatment costs(From randomization until end of treatment (maximum up to 56 months).)
- Exploratory endpoints: Duration of hospitalizations(From randomization until end of treatment (maximum up to 57 months).)
- Exploratory endpoints: Febrile infections(From randomization until end of treatment (maximum up to 57 months).)
- Progression-free survival (PFS) assessed by the investigator(Baseline, every 12 weeks after randomization (maximum up to 76 months))
- Overall response rate (ORR)(Baseline, every 12 weeks after randomization (maximum up to 76 months))
- Incidence of (Serious) Adverse events ((S)AEs)(From date of informed consent to +30 days from last application of study medication (maximum up to 57 months))
- Blood count: Hemoglobin(From date of informed consent to +30 days from last application of study medication (maximum up to 57 months))
- Blood count: Leukocytes(From date of informed consent to +30 days from last application of study medication (maximum up to 57 months))
- Overall survival (OS)(Time from randomization to date of death (maximum up to approximately 76 months))
- Clinical chemistry: Aspartate transaminase (AST)(From date of informed consent to +30 days from last application of study medication (maximum up to 57 months))
- Clinical chemistry: Bilirubin total(From date of informed consent to +30 days from last application of study medication (maximum up to 57 months))
- Clinical benefit rate (CBR)(Baseline, every 12 weeks after randomization (maximum up to 76 months))
- Blood count: Platelet Count(From date of informed consent to +30 days from last application of study medication (maximum up to 57 months))
- Blood count: Absolute Neutrophil Count(From date of informed consent to +30 days from last application of study medication (maximum up to 57 months))
- Clinical chemistry: Alkaline Phosphatase(From date of informed consent to +30 days from last application of study medication (maximum up to 57 months))
- Patient-reported health-related quality of life (QoL): FACT-B total score(Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).)
- Patient-reported health-related quality of life (QoL): FACT-B subscale functional well-being (FWB)(Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).)
- Patient-reported health-related quality of life (QoL): FACT-B breast cancer subscale (BCS)(Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).)
- Patient-reported health-related quality of life (QoL): FACT-B breast cancer subscale (BCS) score decline(Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).)
- Patient-reported health-related quality of life (QoL): FACT/GOG-Ntx4 subscale(Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).)
- Safety monitoring (coagulation): Coagulation (INR)(From date of informed consent to +30 days from last application of study medication (maximum up to 57 months))
- Patient-reported health-related quality of life (QoL): Trial Outcome Index-Physical/Functional/Breast (TOI-PFB)(Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).)
- Patient-reported health-related quality of life (QoL): FACT-B subscale emotional well-being (EWB)(Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).)
- Exploratory endpoints: Reasons for hospitalizations(From randomization until end of treatment (maximum up to 57 months).)
- Clinical chemistry: Alanine transaminase (ALT)(From date of informed consent to +30 days from last application of study medication (maximum up to 57 months))
- Clinical chemistry: Creatinine (Serum)(From date of informed consent to +30 days from last application of study medication (maximum up to 57 months))
- Left Ventricular Ejection Fraction (LVEF) monitoring(LVEF at baseline, every three months thereafter until end of treatment, then every six months for 24 months thereafter (maximum up to 76 months))
- Patient-reported health-related quality of life (QoL): FACT-B subscale physical well-being (PWB)(Baseline, every three weeks for the first 24 weeks, every three months thereafter (maximum up to 36 months).)
- Exploratory endpoints: Employment status(From randomization until end of treatment (maximum up to 56 months).)
- Exploratory endpoints: Number of hospitalizations(From randomization until end of treatment (maximum up to 57 months).)
研究者
研究点 (1)
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