Clinical trial NCT05529862: Trans-RosaLEE Study: a Biomarker-directed, Translational Study
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Advanced or Metastatic Breast Cancer (BC)
Lead sponsor: Institut Paoli-Calmettes
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2022-09-07
Enrollment: 241
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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 criteria: Inclusion Criteria:

1. Patients included in the RosaLEE study.
2. Patients having read and signed the ICF relative to Trans-RosaLEE.
3. 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.
4. Patient affiliated to the national "Social Security" regimen or beneficiary of this regimen.

Exclusion Criteria:

1. Not enrolled in RosaLEE.
2. Brain metastasis and non-osteolytic bone metastases as only metastatic sites, if no available frozen tumour sample already collected within 3 months before V0.
3. Tumour material not collected before ribociclib + ET initiation.
4. Person subject to a legal protection measure (adult under guardianship, curatorship or safeguard of justice), or unable to give their consent.

Primary outcomes:
measure: Molecular alterations post- versus pre-treatment
timeFrame: At the date of first documented progression, assessed up to 54 months
Secondary outcomes:
measure: Molecular alterations associated with progression free survival
timeFrame: At 3 years after treatment initiation (Ribociclib+hormone therapy)
measure: Molecular alterations pre and post-treatment
timeFrame: At the date of first documented progression, assessed up to 54 months
measure: Pre treatment molecular alterations associated with tumor response
timeFrame: At 3 years after treatment initiation (Ribociclib+hormone therapy)
measure: Molecular alterations therapeutically actionable
timeFrame: At the date of first documented progression, assessed up to 54 months
measure: Percentage of patients with molecular alterations therapeutically actionable
timeFrame: Through study completion, an average of 54 months
measure: Percentage of patients with modification of the therapeutic strategy derived from the molecular profiling
timeFrame: Through study completion, an average of 54 months
measure: IHC profile ER
timeFrame: At the date of first documented progression, assessed up to 54 months
measure: IHC profile PgR
timeFrame: At the date of first documented progression, assessed up to 54 months
measure: IHC profile HER2
timeFrame: At the date of first documented progression, assessed up to 54 months
measure: Molecular subtypes PAM50
timeFrame: At the date of first documented progression, assessed up to 54 months
Other outcomes:
Locations:
city: Marseille
country: France
facility: Institut Paoli Calmettes
Study officials:
affiliation: Institut Paoli-Calmettes
name: François Bertucci, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: