Trans-RosaLEE Study: a Biomarker-directed, Translational Study of High-throughput Molecular Profiling of HR+/HER2- Metastatic Breast Cancer Treated With Endocrine Therapy and Ribociclib.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 241
- 试验地点
- 1
- 主要终点
- Molecular alterations post- versus pre-treatment
研究概览
简要总结
Hormone receptor (HR)-positive and HER2-negative (HR+/HER2-) metastatic/advanced breast cancer (mBC) is a major public health issue. During the last decades, a therapeutic challenge was to overcome the tumor's resistance to endocrine therapy (ET). Thanks to a better understanding of the molecular mechanisms of this resistance, effective new treatments have been developed, such as Kisqali® (ribociclib), a molecularly targeted therapy. This treatment blocks the growth and division of cancer cells by blocking proteins called CDK4/6 located inside the cell. This treatment, taken in combination with ET, blocks the harmful effect of hormones (estrogen) on cancer cell proliferation, and represent the standard first-line treatment of patients with HR+/HER2- mBC.
But, as with any treatment, it is expected that some patients will have a good response and their disease will be stabilized or even in remission, while other patients will not benefit from treatment and will relapse. In order to make progress, it is necessary to identify pre-therapeutic markers predictive of response to this treatment and the molecular mechanisms of this resistance set up by the tumor before or under the effect of the treatment.
The Trans-RosaLEE study aims to fill this gap by providing high-throughput molecular profiling (DNA and RNA) of a collection of tumor and blood samples from patients with RH+/HER2- mBC scheduled to start treatment with Kisqali® + ET. Samples will be collected just prior to initiation of therapy (pre-therapy) and just after discontinuation of therapy in the event of disease progression (post-therapy).
The main objectives of the TransRosaLEE study are :
- to determine if Kisqali® + ET treatment causes changes in the DNA and/or RNA genes of tumor;
- to identify whether there is a molecular signature that would predict clinical outcome of patients treated with Kisqali® + ET (tumor response, survival);
- to identify alterations in tumor's genes that could be targeted by a specific treatment and that would allow, in case of progression of the disease, to set up a new adapted treatment.
The TransRosaLEE study is a collaborative study between the Paoli-Calmettes Institute (France, Marseille) and the pharmaceutical group Novartis. It will take place in up to 90 healthcare institutions in France, and 241 patients will be enrolled. It is closely linked to the non-interventional study RosaLEE promoted by Novartis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 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 included in the RosaLEE study.
- •Patients having read and signed the ICF relative to Trans-RosaLEE.
- •Tumour material: primary and/or metastatic tumour sample, either available as frozen and collected within 3 months before V0, or newly collected before ribociclib + ET treatment initiation.
- •Brain metastases and non-osteolytic bone metastases will be considered as non-collectable/biopsable.
- •Patient affiliated to the national "Social Security" regimen or beneficiary of this regimen.
排除标准
- •Not enrolled in RosaLEE.
- •Brain metastasis and non-osteolytic bone metastases as only metastatic sites, if no available frozen tumour sample already collected within 3 months before V
- •Tumour material not collected before ribociclib + ET initiation.
- •Person subject to a legal protection measure (adult under guardianship, curatorship or safeguard of justice), or unable to give their consent.
研究组 & 干预措施
Locally advanced or metastatic Breast Cancer Women
Study Procedures:
- Additional tumour sampling during the pre-treatment biopsy scheduled as per routine care,
- A post-treatment tumour biopsy,
- One pre-treatment and one post-treatment blood sampling.
干预措施: Pre-treatment biopsy (Genetic)
Locally advanced or metastatic Breast Cancer Women
Study Procedures:
- Additional tumour sampling during the pre-treatment biopsy scheduled as per routine care,
- A post-treatment tumour biopsy,
- One pre-treatment and one post-treatment blood sampling.
干预措施: Post treatment biopsy (Genetic)
Locally advanced or metastatic Breast Cancer Women
Study Procedures:
- Additional tumour sampling during the pre-treatment biopsy scheduled as per routine care,
- A post-treatment tumour biopsy,
- One pre-treatment and one post-treatment blood sampling.
干预措施: Pre treatment blood sampling (Genetic)
Locally advanced or metastatic Breast Cancer Women
Study Procedures:
- Additional tumour sampling during the pre-treatment biopsy scheduled as per routine care,
- A post-treatment tumour biopsy,
- One pre-treatment and one post-treatment blood sampling.
干预措施: Post treatment blood sampling (Genetic)
结局指标
主要结局
Molecular alterations post- versus pre-treatment
时间窗: At the date of first documented progression, assessed up to 54 months
Occurrence of molecular alterations, including DNA copy number, gene mutations by WES and messenger RNA (mRNA) expression profiles by RNA-seq in paired post- versus pre-treatment samples.
次要结局
- Molecular alterations associated with progression free survival(At 3 years after treatment initiation (Ribociclib+hormone therapy))
- Molecular alterations pre and post-treatment(At the date of first documented progression, assessed up to 54 months)
- Molecular alterations therapeutically actionable(At the date of first documented progression, assessed up to 54 months)
- Percentage of patients with molecular alterations therapeutically actionable(Through study completion, an average of 54 months)
- Percentage of patients with modification of the therapeutic strategy derived from the molecular profiling(Through study completion, an average of 54 months)
- IHC profile ER(At the date of first documented progression, assessed up to 54 months)
- Molecular subtypes PAM50(At the date of first documented progression, assessed up to 54 months)
- IHC profile HER2(At the date of first documented progression, assessed up to 54 months)
- Pre treatment molecular alterations associated with tumor response(At 3 years after treatment initiation (Ribociclib+hormone therapy))
- IHC profile PgR(At the date of first documented progression, assessed up to 54 months)