A Phase 2 Study of Lapatinib in Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 87
- 试验地点
- 9
- 主要终点
- Objective Response Rate
研究概览
简要总结
In this research study we are studying the effects of the combination of lapatinib plus Herceptin in subjects with breast cancer that has spread outside of the breast. We are also studying whether positron emission tomography (PET/CT) scans can predict which participants will benefit from the study treatment. Finally, we are studying genes and proteins in the tumor tissue that may lead to sensitivity or resistance to Herceptin, and to the combination of Herceptin plus lapatinib. Lapatinib is a compound that may stop cancer cells from growing. Other research studies suggest that lapatinib in combination with Herceptin may help to shrink or stabilize breast cancer.
详细描述
- Participants will be asked to undergo a biopsy of an area of the body where the cancer has spread.
- Participants will be given a study medication-dosing calendar for each treatment cycle. Each treatment cycle lasts four weeks during which time you will be taking lapatinib, once per day.
- Participants will receive Herceptin once every week or once every 3 weeks through a vein.
- During all treatment cycles a physical exam will be performed and questions about the participants general health will be asked. Blood tests including chemistry and hematology will be performed to measure additional effect of the study drug and disease status. Photographs may be taken of the tumor to assess the response of the tumor to treatment.
- CT scans will be repeated every 8 weeks to assess the effect of the study treatment on the cancer. Either a MUGA scan or echocardiogram will be performed 8 weeks and 16 weeks after the participant starts the study treatment.
- Participants will remain on this research study for as long as they are benefiting from the study treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Histologically or cytologically confirmed invasive breast cancer, with stage IV disease
- •HER2-positive breast cancer, defined as 3+ staining by IHC or gene amplification by FISH
- •Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension
- •Willingness to undergo a research biopsy of recurrent or metastatic disease
- •Prior chemotherapy treatment must be discontinued for at least 2 weeks prior to study entry.
- •Completed radiation therapy at least 7 days prior to beginning protocol treatment
- •Cohort 1: No prior chemotherapy for advanced breast cancer; no prior trastuzumab in the advanced breast cancer setting; nor prior treatment with lapatinib or other HER2-directed therapy other than trastuzumab
- •Cohort 2: Up to two prior chemotherapy regimens for the treatment of advanced breast cancer; no prior treatment with lapatinib or other HER2-directed therapy except for trastuzumab
- •18 years of age or older
- •Life expectancy of greater than 12 weeks
- •ECOG Performance Status 0-2
- •Normal organ and marrow function as outlined in protocol
- •Cardiac ejection fraction, as assessed by either MUGA scan or echocardiogram greater than or equal to 50%
- •Able to take oral medications
排除标准
- •Patients may not be receiving any other investigational agents or concurrent chemotherapy or hormonal therapy for treatment of metastatic disease
- •Active brain metastases
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or other agents used in this study
- •Clinically significant malabsorption syndrome
- •Uncontrolled intercurrent illness
- •Pregnant or breastfeeding women
- •Concurrent use of the medications listed in the protocol because of possible interaction with lapatinib
研究组 & 干预措施
Cohort 1
This cohort is made up of participants without prior trastuzumab for MBC. Adjuvant or neoadjuvant trastuzumab was allowed, if the interval from trastuzumab completion to recurrence exceeded 1 year.
1000 mg daily Lapatinib
2 mg/kg weekly or 6 mg/kg every 3 week dose of trastuzumab
干预措施: Lapatinib (Drug)
Cohort 1
This cohort is made up of participants without prior trastuzumab for MBC. Adjuvant or neoadjuvant trastuzumab was allowed, if the interval from trastuzumab completion to recurrence exceeded 1 year.
1000 mg daily Lapatinib
2 mg/kg weekly or 6 mg/kg every 3 week dose of trastuzumab
干预措施: Herceptin (Drug)
Cohort 2
This cohort is made up of participants with one to two lines of chemotherapy for metastatic disease with at least one trastuzumab-containing regimen or patients who recurred within 12 months of adjuvant or neoadjuvant trastuzumab with up to one line of metastatic trastuzumab-based therapy
1000 mg daily Lapatinib
2 mg/kg weekly or 6 mg/kg every 3 week dose of trastuzumab
干预措施: Lapatinib (Drug)
Cohort 2
This cohort is made up of participants with one to two lines of chemotherapy for metastatic disease with at least one trastuzumab-containing regimen or patients who recurred within 12 months of adjuvant or neoadjuvant trastuzumab with up to one line of metastatic trastuzumab-based therapy
1000 mg daily Lapatinib
2 mg/kg weekly or 6 mg/kg every 3 week dose of trastuzumab
干预措施: Herceptin (Drug)
结局指标
主要结局
Objective Response Rate
时间窗: 8 weeks
The objective response rate is the percentage of participants achieving complete response (CR) or partial response (PR) as the best response recorded on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. CR and PR must meet the following lesion criteria without having any new lesions as well: Target Lesion: (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Non-Target Lesion: (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). Non-CR/Non-Progressive Disease: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have PR in target lesion.
次要结局
- 3-Year Overall Survival(Up to 93 months)
- Clinical Benefit Rate(Up to 93 months)
- Top 3 Most Common Treatment RelatedToxicities(Up to 93 months)
- Sites of First Progression(Up to 93 months)
- Median Time to Progression(Up to 93 months)
研究者
Nancy Lin, MD
Assistant Professor of Medicine
Dana-Farber Cancer Institute