Phase II Study of Denosumab to Define the Role of Bone Related Biomarkers in Breast Cancer Bone Metastasis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- The Effect of Denosumab in Reducing Circulating Tumor Cells (CTCs) Among Breast Cancer Patients With Bone Metastases.
研究概览
简要总结
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.
详细描述
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:
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
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
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.
干预措施: Denosumab (Drug)
结局指标
主要结局
The Effect of Denosumab in Reducing Circulating Tumor Cells (CTCs) Among Breast Cancer Patients With Bone Metastases.
时间窗: Baseline, week 4
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.
次要结局
- The Changes of Epithelial-mesenchymal Transition (EMT) in CTCs(Baseline, week 4)
- The Changes in Urine N-telopeptide Level(Baseline up to week 13)