Trans-RosaLEE Study: a Biomarker-directed, Translational Study

Condition(s) studied

Investigational drug(s) / intervention(s)

Pre-treatment biopsy: Pre-treatment fragments will be collected during the biopsy visit organised as part of routine medical practice, prior to the start of treatment with ribociclib + ET

Post treatment biopsy: Post-treatment fragments will be collected during a biopsy visit specifically planned for Trans-RosaLEE study.

Pre treatment blood sampling: Sampling of 4 EDTA Tubes (4ml) and 2 Streck tubes (10ml)

Post treatment blood sampling: Sampling of 2 Streck tubes (10ml)

Study summary

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.

Eligibility

Primary outcome measure(s)

• Molecular alterations post- versus pre-treatment — 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.

Trial sites (1)

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