Biomarker Study of the Antitumoral Activity of Denosumab in the Pre- Operative Setting of Early Breast Cancer

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追踪信息

首次提交日期 ^ICMJE

September 4, 2018

首次发布日期e ^ICMJE

October 1, 2018

最后更新发布日期

October 1, 2018

预计研究开始日期 ^ICMJE

July 5, 2018

预计主要完成日期

July 5, 2019 (主要结果测量的最终数据收集日期)

目前主要观察指标 ^ICMJE

Antiproliferative and/or pro-apoptotic activity of denosumab[ Time Frame: From first biopsy until surgery intervention, which is around four weeks after enrolment ]

Changes in the percentage of tumor cells expressing Ki67 and/or cleaved caspase 3 between Biopsy A and Biopsy B.

原始主要观察测量 ^ICMJE

与当前相同

目前的二级观察 ^ICMJE

Correlation between antiproliferative activity of denosumab and Rank/RankL expression[ Time Frame: From first biopsy until surgery intervention, which is around four weeks after enrolment ]
Modified ratio of Rank/RankL: MR={log(RANK) -1.2} / log(RANKL) as described in Palafox et al [10].
Differential antiproliferative activity of denosumab among the different phenotypes of breast cancers.[ Time Frame: From first biopsy until surgery intervention, which is around four weeks after enrolment ]
Ki67 estimations for each phenotype
Differential antiproliferative activity of denosumab among pre and post menopausal patients[ Time Frame: From first biopsy until surgery intervention, which is around four weeks after enrolment ]
Ki67 estimations for each menopausal group
Safety of denosumab and biopsy procedures in terms of Frequency of adverse events (CTCAE V4.)[ Time Frame: From first biopsy until surgery intervention, which is around four weeks after enrolment ]
Frequency of adverse events derived from denosumab treatment and biopsy procedures

描述性信息

简略标题 ^ICMJE

Biomarker Study of the Antitumoral Activity of Denosumab in the Pre- Operative Setting of Early Breast Cancer

正式标题 ^ICMJE

An Open Label Biomarker Pilot Study of the Antitumoral Activity of Denosumab in the Pre- Operative Setting of Early Breast Cancer

简要概况

This is a biomarker study designed to test the preclinically generated hypothesis of anti-tumoral activity of denosumab in patients with early breast cancer candidates a tumour excision

详细说明

This is a biomarker study designed to test in patients the preclinically generated hypothesis of anti-tumoral activity of denosumab.The main objective is to demonstrate the antiproliferative and/or pro-apoptotic activity of denosumab in early breast cancer. Other endpoints are to correlate denosumab activity with RANK and RANKL expressions through mRNA and protein; to characterize the differential antiproliferative activity of denosumab between different phenotypes of breast cancer; to identify biomarkers, to identify global changes in gene expression and validate the activity of RANKL antibody in clinical samples. A total of 60 patients with early breast cancer (Stages I and II) candidates to tumor excision as first therapeutic approach will be randomized 2:1, a treatment arm that will receive two doses of denosumab following diagnosis, and a control arm that will not receive treatment. At least 24 patients with hormone receptor negative breast cancer and 24 premenopausal patients will be included in the study.

研究类型 ^ICMJE

Interventional

研究阶段

Early Phase 1

研究设计 ^ICMJE

分配: Randomized
干预模型: Parallel Assignment
干预模型描述: This is a parallel two arms trial randomized in 2:1 proportions to intervention group vs control group. . At least 24 patients with hormone receptor negative breast cancer and 24 premenopausal patients will be included in the study so allocation of patients without any of these two characteristics will be restricted depending on the overall characteristics of the included population
盲法: Interventional
盲法描述:
主要目的: Treatment

适用条件 ^ICMJE

干预项目 ^ICMJE

Drug: Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]
Two injections on days 1 and 8 previous to surgery breast cancer excision

研究工具

Experimental: Denosumab
Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]
No Intervention: Control
Control group

招募信息

招募状态 ^ICMJE

Recruiting

预计入组 ^ICMJE

原始预计入组 ^ICMJE

与当前相同

预计研究完成日期

February 5, 2020

预计主要完成日期

July 5, 2019 (主要结果测量的最终数据收集日期)

合格标准 ^ICMJE

Inclusion Criteria: - Understand and sign Informed Consent for this study. - Women ≥ than 18 years, (the inclusion process will be modified to recruit at least 24 premenopausal patients). - Capable, under investigator judgment, to understand the non-therapeutic nature of the study. - Diagnosed with invasive breast cancer in early, curable, stage (I or II) candidate to radical surgery as first therapeutic approach. - Her2 negative receptor status. - Any estrogen, progesterone status (the inclusion process will be modified to recruit at least 24 patients with TNBC tumors). - No previous systemic treatment for any malignancy. - No ongoing treatment with denosumab or bisphosphonates. - Tumour amenable for baseline Biopsy and punch-Biopsy after excision. - Adequate Serum calcium or albumin-adjusted serum calcium ≥ 2.0 mmol/L (8.0 mg/dL) and ≤ 2.9 mmol/L (11.5 mg/dL) - No prior history or current evidence of osteonecrosis of the jaw - No Active dental or jaw condition which requires oral surgery, including tooth extraction. Noplanned invasive dental procedures. - General Laboratory test within normality or with non-relevant deviations of normality as per investigator judgment. - Patients must have a normal organ and bone marrow function as defined local standards: Leukocytes, Absolute neutrophil count, Platelets, Total bilirubin, AST/ALT/GOT/GPT, Creatinine, Creatinine clearance, Magnesium, Phosphorus. - Subject with reproductive potential must be willing to use, in combination with her partner, 2 acceptable methods of effective contraception or practice sexual abstinence throughout the study and continue for 6 months after study duration. Subjects who are surgically sterile (e.g. history of bilateral tubal ligation, hysterectomy) or whose sexual partner is sterile (e.g. history of vasectomy) are not required to use additional contraceptive measures". Exclusion Criteria: - Invasive breast cancer non-amenable to surgical excision as first therapeutic approach. - HER2-positive Breast Cancer - Metastatic breast cancer or other condition that recommends other treatment than surgery as the primary therapeutic approach. - Prior systemic treatment for any malignancy. - Treatment with denosumab contraindicated. - Bleeding diathesis or other concomitant condition that contraindicate inclusion in the study as per investigator judgment. - High risk of ONJ or hypocalcemia: - Inadequate Serum calcium or albumin-adjusted serum calcium < 2.0 mmol/L (8.0 mg/dL) or > 2.9 mmol/L (11.5 mg/dL). - Prior history or current evidence of osteonecrosis of the jaw - Active dental or jaw condition which requires oral surgery, including tooth extraction. Planned invasive dental procedures. - Subject has known sensitivity to any of the products to be administered during the study (e.g., mammalian derived products, calcium, or vitamin D). - Subject is pregnant or breast feeding or planning to become pregnant / breastfeed while on study through 6 months after the end of treatment. - Subject 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 oftreatment. - Patients have prior history or current evidence of osteonecrosis or osteomyelitis of the jaw. - Patients have active dental or jaw condition which requires oral surgery, including tooth extraction. - Patients have non-healed dental or oral surgery, including tooth extraction. - Patients with planned invasive dental procedures for the course of the study. - Ongoing treatment with denosumab or bisphosphonates

性别

参与研究的性别:

Female

年龄

最小年龄：18 Years ，最大年龄：N/A

接受健康的志愿者

没有

可入组国家 ^ICMJE

Spain

管理信息

数据检测委员会

研究涉及美国FDA监管的产品

研究美国FDA监管的药品: No
研究涉及美国FDA监管的设备产品: No

IPD 共享声明

计划分享 IPD:

责任方

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研究赞助商 ^ICMJE

Institut Català d'Oncologia

合作者 ^ICMJE

研究员 ^ICMJE

PRS 账户

验证日期

September 2018

^ICMJE 国际医学期刊编辑委员会和世界卫生组织 ICTRP 要求的元素

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