Trans-RosaLEE Study: a Biomarker-directed, Translational Study (TransRosaLEE)

• ClinicalTrials.gov Identifier: NCT05529862
• Recruitment Status: Recruiting
• First Posted: September 7, 2022
• Last Update Posted: June 23, 2023
• Sponsor: Institut Paoli-Calmettes
• Collaborator: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Institut Paoli-Calmettes

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced or Metastatic Breast Cancer (BC)	Genetic: Pre-treatment biopsy; Genetic: Post treatment biopsy; Genetic: Pre treatment blood sampling; Genetic: Post treatment blood sampling	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 241 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• 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.
• Actual Study Start Date: June 20, 2023
• Estimated Primary Completion Date: April 1, 2026
• Estimated Study Completion Date: October 1, 2027

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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.

Genetic: 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; Genetic: Post treatment biopsy; Post-treatment fragments will be collected during a biopsy visit specifically planned for Trans-RosaLEE study.; Genetic: Pre treatment blood sampling; Sampling of 4 EDTA Tubes (4ml) and 2 Streck tubes (10ml); Genetic: Post treatment blood sampling; Sampling of 2 Streck tubes (10ml)

Outcome Measures

Primary Outcome Measures :

1. Molecular alterations post- versus pre-treatment [ Time Frame: 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.

Secondary Outcome Measures :

1. Molecular alterations associated with progression free survival [ Time Frame: At 3 years after treatment initiation (Ribociclib+hormone therapy) ]
   Occurrence of molecular alterations in pre-treatment samples, such as DNA copy number alterations and mutational profiles analysed by WES, and mRNA expression profiles analysed by RNA-seq, associated with progression free survival.
2. Molecular alterations pre and post-treatment [ Time Frame: 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 mRNA expression profiles by RNA-seq in the totality of pre- and post-treatment samples (paired and unpaired).
3. Pre treatment molecular alterations associated with tumor response [ Time Frame: At 3 years after treatment initiation (Ribociclib+hormone therapy) ]
   Occurrence of molecular alterations in pre-treatment samples, such as DNA copy number alterations and mutational profiles analysed by WES and mRNA expression profiles analysed by RNA-seq, associated with tumour response according to RECIST 1.1 guidelines (complete and partial responses).
4. Molecular alterations therapeutically actionable [ Time Frame: At the date of first documented progression, assessed up to 54 months ]
   Occurrence of molecular alterations in pre- and post-treatment samples, such as DNA copy number alterations and mutational profiles analysed by WES, which are therapeutically actionable according to the ESCAT scale.
5. Percentage of patients with molecular alterations therapeutically actionable [ Time Frame: Through study completion, an average of 54 months ]
   Percentage of patients with molecular alterations such as DNA mutations and/or copy number alterations by WES, which are therapeutically actionable according to the ESCAT scale, in pre- and post-treatment samples.
6. Percentage of patients with modification of the therapeutic strategy derived from the molecular profiling [ Time Frame: Through study completion, an average of 54 months ]
   Percentage of patients for which modification of the therapeutic strategy could have been derived from the molecular profiling of the post-treatment samples compared to that of the pre-treatment samples, according to the ESCAT scale.
7. IHC profile ER [ Time Frame: At the date of first documented progression, assessed up to 54 months ]
   IHC profile ER of pre- and post-treatment samples.
8. IHC profile PgR [ Time Frame: At the date of first documented progression, assessed up to 54 months ]
   IHC profile PgR of pre- and post-treatment samples.
9. IHC profile HER2 [ Time Frame: At the date of first documented progression, assessed up to 54 months ]
   IHC profile HER2 of pre- and post-treatment samples.
10. Molecular subtypes PAM50 [ Time Frame: At the date of first documented progression, assessed up to 54 months ]
    Molecular subtypes PAM50 of pre- and post-treatment samples.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: DOMINIQUE GENRE; 0491223778; drci.up@ipc.unicancer.fr

Locations

France

Institut Paoli Calmettes; Recruiting

Marseille, France

Contact: Dominique Genre, MD 0033491223778 drci.up@ipc.unicancer.fr

Sponsors and Collaborators

Institut Paoli-Calmettes

Novartis Pharmaceuticals

Investigators

• Principal Investigator: François Bertucci, MD PhD; Institut Paoli-Calmettes

More Information

• Responsible Party: Institut Paoli-Calmettes
• ClinicalTrials.gov Identifier: NCT05529862
• Other Study ID Numbers: TransRosaLEE-IPC 2021-075
• First Posted: September 7, 2022
• Last Update Posted: June 23, 2023
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases