Phase II Short-term Adjuvant Therapy and Biomarker Studies With Targeted Agents in Women With Estrogen Receptor Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 2
- 主要终点
- Change in Ki-67 in Breast Tissue of High-Risk Women
研究概览
简要总结
The goal of this clinical research study is to learn if dasatinib can help prevent breast cancer from developing in the unaffected breast.
Dasatinib is designed to decrease the activity of one or more proteins that are responsible for the uncontrolled growth of tumor cells.
This is an investigational study. Dasatinib is FDA approved and commercially available for the treatment of leukemia. Its use in breast cancer patients in investigational.
Up to 66 patients will take part in this multicenter study. Up to 60 will be enrolled at MD Anderson.
详细描述
Study Drug Administration:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 3 study groups:
- If you are in Group 1, you will take dasatinib 40mg once a day by mouth with water.
- If you are in Group 2, you will take dasatinib 80mg once a day by mouth with water.
- If you are in Group 3, you will not receive dasatinib.
You will be given a study drug diary to complete. In the diary, you will record when you take the study drug.
Study Visits:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 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
- •Histological confirmation of ER negative breast carcinoma (defined as less than 10%), stage I, II, or III
- •Completed all adjuvant therapy including (if indicated) endocrine, trastuzumab, radiation therapy
- •At least 18 years of age.
- •Female: A female is eligible to enter and participate in the study if she is of: a. Non-childbearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation, hysterectomy alone, hysterectomy and bilateral salpingo-oophorectomy, bilateral salpingo-oophorectomy alone or women who are post-menopausal); or b. Childbearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility. This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate), has a negative serum pregnancy test at screening, and agrees to one of the following where considered acceptable to the local IRB/IEC: • Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm).
- •(Continued from above) • Abstinence from sexual intercourse from 2 weeks prior to administration of the investigational product, throughout the active study treatment period. • Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject. • Any intrauterine device (IUD). • Barrier methods including diaphragm or condom with a spermicide.
- •Able to swallow and retain oral medication.
- •ECOG (Eastern Cooperative Oncology Group) performance status 0 to
- •Provided written informed consent.
- •Adequate bone marrow function: Hemoglobin >/= 9 gm/dL. • Absolute granulocyte count >/= 1,500/mm^3 (1.5 x 10^9/L). • Platelets >/= 75,000/mm^3 (100 x 10^9/L).
- •Serum creatinine < 1.4 mg/dL or calculated creatinine clearance (CrCl) >/= 30 mL/min
- •Total bilirubin </= 1.5 times the upper limit of the reference range
- •Aspartate and alanine transaminase (AST or ALT) </= 2 times the upper limit of the reference range.
- •Patients must have a baseline ECG with QTcF within the normal range within 28 days prior to registration.
- •Normal mammogram of unaffected breast within 12 months prior to study entry.
排除标准
- •Unwillingness to undergo RPFNA.
- •Contraindication to RPFNA including breast implant(s), bilateral radiation, anticoagulation (excluding those on 81mg aspirin).
- •Concurrent medical condition that would increase drug toxicity: Pleural or pericardial effusion, coagulation or platelet function disorder, ongoing or recent (less than 3 months gastrointestinal bleeding)
- •Uncontrolled angina, congestive heart failure, MI (within last 6 months), congenital long QT syndrome, history of clinically significant ventricular arrhythmia, prolonged QTcF interval on pre-entry EKG (greater than normal range)
- •Hypokalemia or hypomagnesemia if it cannot be corrected
- •Is a pregnant or lactating female.
- •Has evidence of recurrent or metastatic (Stage IV) breast cancer.
- •Is considered medically unfit for the study by the investigator as a result of the medical interview, physical exam, or screening investigations.
- •Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to dasatinib
- •Has received treatment with any investigational drug in the previous 4 weeks.
- •Has received chemotherapy, immunotherapy, biologic therapy or endocrine therapy within the past 12 weeks.
- •Is currently receiving oral steroid treatment (inhaled steroids are permitted)
- •Oral estrogen, progesterone, testosterone therapy within last 3 months.
- •Concomitant Medications: Drugs that are considered category D (Consider therapy modification) and X (Avoid combination) using the Lexicomp database are prohibited. Concomitant drugs that fall into categories A (No known interaction), B (no action needed) and C (monitor therapy) are allowed.
研究组 & 干预措施
Group 1: Dasatinib 40 mg
Dasatinib 40 mg by mouth once a day for 3 months (+/- 7 days), At the end of the 3 months (+/- 7 days) participants undergo a repeat FNA and blood collection for the same marker analyses.
干预措施: Dasatinib (Drug)
Group 2: Dasatinib 80 mg
Dasatinib 80 mg by mouth once a day for 3 months (+/- 7 days). At the end of the 3 months (+/- 7 days) participants undergo a repeat FNA and blood collection for the same marker analyses.
干预措施: Dasatinib (Drug)
结局指标
主要结局
Change in Ki-67 in Breast Tissue of High-Risk Women
时间窗: up to 3 months
Change in Ki-67 measured in baseline and month 3 using contralateral breast Fine Needle Aspiration (FNA) samples. Samples evaluated by immunohistochemistry (IHC). Baseline and follow up Ki-67 values presented in percentage (%) of cell positive, change reflects difference in percentage. Ki-67 is measured as a continuous variable and a one-way ANOVA followed by Dunnett's multiple comparison test comparing the change of Ki-67 of each of the three treated groups with control.
次要结局
- To Evaluate Dasatinib Induced Modulation of Biomarker in the Serum Including Insulin Like Growth Factor (IGF) Pathway(up to 3 months)