Denosumab for Breast Cancer With Bone Mets
Phase II Study of Denosumab to Define the Role of Bone Related Biomarkers in Breast Cancer Bone Metastasis
The goal of this clinical research study is to learn if denosumab in combination with a hormonal drug can help lower the number of circulating tumor cells (CTCs) in patients with breast cancer that has spread to the bone. The safety of this combination will also be studied.
This is an investigational study. Denosumab is FDA approved and commercially available to prevent bone-related events caused by breast cancer that has spread to the bone. Using denosumab to lower CTCs in patients with breast cancer that has spread to the bone is investigational.
You may have the option of continuing denosumab after the study ends.
Up to 35 patients will take part in this study. All will be enrolled at MD Anderson.
研究概览
详细说明
Study Drug Administration:
If you are found to be eligible to take part in this study, you will receive denosumab through a needle under your skin on Day 1 of each 28-day study cycle.
Starting on Day 1 of week 4, you will also begin taking a hormonal drug. The study doctor will choose the hormonal drug you receive based on your previous hormonal therapy for breast cancer. The study doctor will give you instructions for taking your hormonal drug.
Study Visits:
On Day 1 of week 4:
- You will have a physical exam
- Blood (about 3 tablespoons) will be drawn for routine tests
- Blood (about 5 teaspoons) will be drawn for CTC testing and to check your immune system.
- Urine will be collected to test for a biomarker that is used to measure the rate of bone breakdown.
- If the study doctor thinks it is needed, you will have a PET scan, a bone scan, or an MRI to check the status of the disease.
On Day 1 of Cycle 2 and Cycle 3, blood (about 1 teaspoon) will be drawn for routine tests.
Length of Study:
You may receive the denosumab and hormonal therapy combination for up to 13 weeks. You will be taken off study if the disease gets worse or intolerable side effects occur.
End of Study Visit:
After your last dose of the study drug, the following tests and procedures will be performed:
- You will have a physical exam.
- Blood (about 3 tablespoons) will be drawn for routine tests.
- Blood (about 5 teaspoons) will be drawn for CTC testing and to check your immune system.
- Urine will be collected to test for a biomarker that is used to measure the rate of bone breakdown.
- If the study doctor thinks it is needed, you will have a PET scan, a bone scan, or an MRI to check the status of the disease.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Texas
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Houston、Texas、美国、77030
- University of Texas MD Anderson Cancer Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Patients have histological confirmation of breast carcinoma.
- Patients have progressive metastatic disease with predominantly bone metastasis with 1 or more lesions and at least 1 bone lesion has pathological confirmation, have not been treated or have been treated with any prior therapies (including bisphosphonate treatment and/or radiation therapy). Patients can have soft tissue involvement (Lymph node and skin) and/or metastatic lesions at major organ sites (i.e. lung, liver, etc).
- Patients have positive ER expression in the primary tumor site by IHC (defined as >/=10%) (PR status is not required)
- Adequate hematologic function: 1)Absolute neutrophil count (ANC) >/= 1.0 x 10^9/L, 2) Platelet count >/= 50 x 10^9/L, 3) Hemoglobin >/= 9.0 g/dL
- Adequate cardiac function (LVEF >/= 45%) if patient has known cardiac dysfunction history
- Adequate Renal function: Calculated creatinine clearance >30 ml/min
- Adequate Hepatic function: 1) Aspartate aminotransferase (AST) </= 2.5 x ULN; 2) Alanine aminotransferase (ALT) </= 2.5 x ULN; 3) Alkaline phosphatase (Alp) </= 2.5 x ULN; 4) Total bilirubin </= 2.0 x ULN
- Serum calcium or albumin-adjusted serum calcium >/=2.0mmol/L (8.0mg/dL) and </= 2.9 mmol/L (11.5mg/dL)
- Patients have ability and willingness to sign written informed consent.
- Patients are 18 years of age or older.
- Female patients of childbearing potential (A female not free from menses > 2 years or not surgically sterilized) must be willing to use highly effective contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study. Highly effective contraception, defined as male condom with spermicide, diaphragm with spermicide, intra-uterine device. Highly effective contraception must be used by both sexes during the study and must be continued for 5 months after the last dose of denosumab.
- Female patients of childbearing potential must have negative serum pregnancy test </= 21 days prior to starting study treatment.
- Patients have CTC >/=3.
Exclusion Criteria:
- Patients have known sensitivity to any of the products to be administered during the study (e.g., mammalian derived products, calcium, or vitamin D).
- Patients receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, radiation therapy and biological therapy) while taking study medication. However, patients receiving CDK4/6 inhibitor or mTOR inhibitor as a standard of care while on study is permitted.
- Patients with metastatic sites that requires chemotherapy.
- Patients with active infection and requiring IV or oral antibiotics.
- Patients with concurrent disease or condition that would make them inappropriate for study participation, or any serious medical disorder that would interfere with patients' safety.
- Patients have HER2-positive breast carcinoma (IHC staining more than 3+ or HER2 gene amplification by FISH)
- Patient is pregnant or breast feeding, or planning to become pregnant within 5 months after the end of treatment.
- Patient is of child bearing potential and is not willing to use, in combination with her partner, two highly effective methods of contraception or abstinence during treatment and for 5 months after the end of treatment.
- Male patients.
- Patients have prior history or current evidence of osteonecrosis/osteomyelitis of the jaw.
- Patients have active dental or jaw condition which requires oral surgery, including tooth extraction.
- Patients have non healed dental/oral surgery, including tooth extraction.
- Patients planned invasive dental procedures.
- Patients experiencing a visceral crisis including severe organ dysfunction as assessed by > Gr 2 symptomatic toxicities, laboratory studies, and/ or rapid progression of disease originating from visceral metastasis.
- Patients that have received the study medication (Xgeva/Prolia).
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Denosumab
Participants receive a single subcutaneous (SC) administration of Denosumab 120 mg every 4 weeks (+/- 5days).
Starting week 5, in addition to receiving Denosumab every 4 weeks, participants receive a hormonal agent chosen by each physician, excluding the agent that participants received at adjuvant therapy setting.
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120 mg subcutaneously on Day 1 of every 28 day cycle.
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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The Effect of Denosumab in Reducing Circulating Tumor Cells (CTCs) Among Breast Cancer Patients With Bone Metastases.
大体时间:Baseline, week 4
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The difference in number of CTCs in 7.5 ml whole blood from baseline to week4.
CTC reduction from baseline to week4 is statistically analyzed using the two-sided paired t-test with the significance level of 0.05.
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Baseline, week 4
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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The Changes of Epithelial-mesenchymal Transition (EMT) in CTCs
大体时间:Baseline, week 4
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The change in Her2, Muc-1, GA733-2 (EpCAM), Twist, Akt, PI3K and ALDH-1 in CTCs after 1 st cycle of treatment with denosumab.
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Baseline, week 4
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The Changes in Urine N-telopeptide Level
大体时间:Baseline up to week 13
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The collection urine is performed at baseline, at week4 and the end of 3rd cycle (week13) to evaluate the level of N-telopeptide.
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Baseline up to week 13
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合作者和调查者
合作者
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
Denosumab的临床试验
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Seoul National University Bundang Hospital未知
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Institut Català d'OncologiaAmgen主动,不招人
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European Organisation for Research and Treatment...Amgen终止
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Arbeitsgemeinschaft medikamentoese TumortherapieAmgen; Assign Data Management and Biostatistics GmbH主动,不招人
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AmgenDaiichi Sankyo, Inc.完全的癌症 | 多发性骨髓瘤 | 骨转移 | 血液系统恶性肿瘤 | 肿瘤学 | 多发性骨髓瘤骨病变美国, 德国, 意大利, 西班牙, 加拿大, 法国, 捷克语, 匈牙利, 大韩民国, 俄罗斯联邦, 英国, 台湾, 澳大利亚, 香港, 新西兰, 奥地利, 斯洛伐克, 葡萄牙, 希腊, 保加利亚, 波兰, 乌克兰, 爱尔兰, 瑞士, 火鸡, 立陶宛, 新加坡, 日本, 马来西亚