Phase II Study of Neratinib in Patients 60 and Older With HER2 Positive Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 7
- 主要终点
- Percent of Participants With Grade 2 or Higher Toxicities
研究概览
简要总结
This phase II trial studies the side effects of and how well neratinib works in treating older patients with stage IV HER2-positive breast cancer. Neratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the safety and tolerability of neratinib in adults age 60 or older with locally advanced or metastatic HER2 over-expressing breast cancer.
SECONDARY OBJECTIVES:
I. To describe the full toxicity profile including all grade toxicities measured by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0.
II. To estimate the rate of all grades of gastrointestinal (GI) toxicities such as diarrhea, nausea, and vomiting.
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance 0-2
- •Life expectancy of greater than 12 weeks
- •Histologically or cytologically proven metastatic breast cancer (metastases can be proven with imaging results in certain circumstances provided that the initial tumor was demonstrated histologically)
- •Stage IV HER2/Neu positive breast cancer patients who failed previous anti-HER2 targeted therapies
- •HER2 positivity as defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
- •If HER2 negative by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), but activating somatic mutations of HER2 gene identified through genomic sequencing including but not limited to the following (Clinical Laboratory Improvement Act [CLIA] certified lab test): missense substitutions (G309A, G309E, S310F, S310Y, S653C, V659E, R678Q, V697L, T733I, L755S, L755P, E757A, D769H, D769Y, D769N, G776V, G776C, V777L, L841V, V842I, R849W, L869R, R896C); insertions/deletions (A775_G776insYVMA aka Y772_A755dup, G776VinsC, G776AinsVGC, G776 insertions, G778_S779insCPG, P780_781insGSP aka G778_P780dup, L755_T759del) and/or HER3 activating mutations; there is no limitation on the number of prior lines of systemic therapy or HER2-targeted therapies (prior neratinib not allowed)
- •Both measurable as well as non-measurable disease will be allowed
- •Hemoglobin >= 9 g/dL (after transfusion, if necessary) within 4 weeks of pre-registration
- •Total bilirubin within normal institutional limits within 4 weeks of pre-registration
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal within 4 weeks of pre-registration
- •Creatinine clearance >= 30 mL/min as calculated by Cockcroft-Gault formula within 4 weeks of pre-registration
- •Baseline left ventricular ejection fraction LVEF >= 50% as evaluated by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
- •All grade >= 2 toxicities other than alopecia from prior therapy have resolved by the time of study commencement
- •Patient must have completed radiation therapy with adequate recovery of bone marrow and organ functions, before starting neratinib
- •Patient with stable or treated brain metastases are eligible; asymptomatic patients with metastatic brain disease who have been on a stable dose of corticosteroids for treatment of brain metastases for at least 14 days are eligible to participate in the study
- •Provide written, informed consent to participate in the study and follow the study procedures
排除标准
- •Prior treatment with neratinib
- •Concurrent usage of other investigational agents, chemotherapy, or hormone therapy; prior chemotherapy, hormonal therapy, targeted therapy, and investigational agents are allowed but all toxicities grade >= 2 must have resolved by the time of study commencement (except alopecia)
- •Any major surgery =< 28 days prior to the initiation of investigational products
- •Received chemotherapy or biologic therapy =< 3 weeks prior to the start of neratinib
- •Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of >= 2, including individuals who currently use digitalis specifically for congestive heart failure), unstable angina, myocardial infarction within 12 month of enrollment or ventricular arrhythmia
- •Concurrent use of digoxin due to cardiac disease; corrected QT (QTc) interval >= 450 milliseconds in men and >= 470 milliseconds in women within 2 weeks of registration or known history of QTc prolongation or Torsades de Pointes
- •Inability to take oral medication
- •Other malignancy within the past 3 years with the exception of: a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) cervix or vulva carcinoma in situ; c) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder, or benign tumors of the adrenal or pancreas
- •Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn?s disease, malabsorption, or grade >= 2 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v.4.0 diarrhea of any etiology at baseline)
- •Known clinically active infection with hepatitis B or hepatitis C virus
- •Evidence of significant medical illness, abnormal laboratory finding or psychiatric illness/social situations that would, in the investigator?s judgment, makes the patient inappropriate for this study
研究组 & 干预措施
Treatment (neratinib)
Patients receive neratinib 240mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Comprehensive Geriatric Assessment (Other)
Treatment (neratinib)
Patients receive neratinib 240mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (neratinib)
Patients receive neratinib 240mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Neratinib (Drug)
Treatment (neratinib)
Patients receive neratinib 240mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
结局指标
主要结局
Percent of Participants With Grade 2 or Higher Toxicities
时间窗: On treatment, 28 days per cycle up to 1 year
Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tables will be created to summarize the toxicities and side effects by organ system, attribution and severity for all participants that receive at least one dose of neratinib. Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for grade 2 or higher toxicities attributed to neratinib.
次要结局
- Rate of Participants With a Dose Reduction(On treatment, up to 48 months)
- Rate of Participants Requiring Hospitalizations(On treatment, up to 48 months)
- Median Overall Survival (OS)(Time from start of treatment to death due to any cause, assessed up to 48 months)
- Count of Participants With Grade 3 or Higher Gastrointestinal (GI) Toxicities Such as Diarrhea, Nausea and Vomiting(On treatment, 28 days per cycle up to 1 year)
- Pharmacokinetics of Steady State Neratinib Concentration Transformed Using a Logarithm Base 2(Day 0 to day 15)
- Tumor Response Using Response Evaluation Criteria in Solid Tumors (RECIST)(Participants are evaluated every 12 weeks, up to 48 months)
- Median Progression-free Survival (PFS) in Months(From the date treatment begins until the first date on which recurrence, progression or death due to any cause, assessed up to 48 months)
- Cancer-specific Geriatric Assessment Score(At day 0 of treatment)