Phase II Study of Doxil and Carboplatin, Plus Herceptin in HER2+ Patients, in Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 136
- 试验地点
- 53
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to determine the ORR associated with Doxil in combination with carboplatin in HER2- (negative) MBC (and with Herceptin in HER2+ MBC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Has metastatic breast cancer with documented HER2- or HER2+ (IHC3+ or FISH+) disease
- •Has measurable MBC, with at least 1 measurable lesion per RECIST criteria (see Section 10). Irradiated lesions cannot be used to assess response but can be used to assess progression.
- •Has had no prior treatment with Doxil or carboplatin; may have had adjuvant Herceptin if treatment was completed more than 1 year prior to study
- •Has had no adjuvant chemotherapy within 1 year prior to study, but may have received prior anthracyclines as adjuvant chemotherapy
- •For taxane-pretreated patients (adjuvant or metastatic), has had no more than 1 prior chemotherapy regimen for MBC
- •For taxane-naïve patients, has had no prior chemotherapy for MBC
- •Has had cumulative doses of < 300 mg/m2 prior doxorubicin or < 450 mg/m2 prior epirubicin
- •Has normal cardiac function as evidenced by a LVEF within institutional normal limits by multiple gated acquisition (MUGA) scan. An echocardiogram (ECHO) may be used if MUGA is not available, but the same test must be used throughout the study to evaluate LVEF.
- •Has an ECOG Performance Status (PS) 0-2 (see Appendix I)
- •Is a male or female greater than or equal to 18 years of age
- •Laboratory Values - Please refer to protocol section 4.2 for specific laboratory values.
- •Has a negative serum pregnancy test within 7 days prior to registration (woman of childbearing potential [WOCBP; not surgically sterilized and between menarche and 1 year postmenopause])
- •If fertile, patient (male or female) has agreed to use an acceptable method of birth control (eg, abstinence, intrauterine device, oral contraceptives, barrier device with spermicide or surgical sterilization) to avoid pregnancy for the duration of the study and for a period of 3 months thereafter.
- •Has signed a Patient Informed Consent Form
- •Has signed a Patient Authorization Form (HIPAA Form)
- •Has a life expectancy of > 3 months
排除标准
- •Has had a myocardial infarction (MI) within 6 months of trial enrollment, or has New York Heart Association (NYHA; see Appendix IV) Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
- •Has a history of hypersensitivity reactions attributed to a conventional formulation of doxorubicin HCL or the components of Doxil
- •Has evaluable only disease; eg, bone only, pleural, peritoneal only disease
- •Is receiving concurrent immunotherapy, hormonal therapy, or radiation therapy. Patients receiving immunosuppressant therapy for autoimmune disease may enroll on the trial after a drug washout period of 2 weeks.
- •Is receiving concurrent investigational therapy or has received such therapy within 30 days
- •Has evidence of brain metastases requiring steroids and/or radiation or any documented leptomeningeal disease
- •Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection or history of uncontrolled seizures, CNS disorders deemed by the Treating Physician to be clinically significant, precluding informed consent
- •Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix), which could affect the diagnosis or assessment of any of the study drugs
- •Is a pregnant or lactating woman
- •Is unable to comply with requirements of study
研究组 & 干预措施
Arm 1
Patients will receive IV Doxil 30 mg/m2 and carboplatin AUC=5 on Day 1 of each cycle. A cycle consists of 28 days. In addition, HER2+ (IHC3+ and FISH+) patients only will receive a one-time loading dose of Herceptin 8 mg/kg IV on Day 1 of Cycle 1 and 4 mg/kg on Day 1 and Day 15 of every cycle thereafter.
干预措施: Pegylated liposomal doxorubicin (Drug)
Arm 1
Patients will receive IV Doxil 30 mg/m2 and carboplatin AUC=5 on Day 1 of each cycle. A cycle consists of 28 days. In addition, HER2+ (IHC3+ and FISH+) patients only will receive a one-time loading dose of Herceptin 8 mg/kg IV on Day 1 of Cycle 1 and 4 mg/kg on Day 1 and Day 15 of every cycle thereafter.
干预措施: Carboplatin (Drug)
Arm 1
Patients will receive IV Doxil 30 mg/m2 and carboplatin AUC=5 on Day 1 of each cycle. A cycle consists of 28 days. In addition, HER2+ (IHC3+ and FISH+) patients only will receive a one-time loading dose of Herceptin 8 mg/kg IV on Day 1 of Cycle 1 and 4 mg/kg on Day 1 and Day 15 of every cycle thereafter.
干预措施: trastuzumab (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: From date of randomization until the date of first documented progression or date of intolerable toxicity, whichever came first, assessed up to 54 months.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective response (OR) = CR + PR.
次要结局
- Duration of Response(From date of randomization until the date of first documented progression or date of intolerable toxicity, whichever came first, assessed up to 54 months.)
- Progression-free Survival (PFS)(30 months)
- 1-year Overall Survival(1 year)