Efficacy of Personalized Tumorogram-based Therapy in Cancer Established From Patient-derived Organoid
- Conditions
- Metastatic Breast Cancer
- Interventions
- Procedure: Biopsy
- Registration Number
- NCT06459791
- Lead Sponsor
- Institut Curie
- Brief Summary
A biopsy of a breast tumor lesion will be performed for processing to establish avatars (patient-derived organoids -PDO). A personalized tumorogram for each patient will be provided, based on the results of the drug screening (= tumor predicted as sensitive, intermediate, resistant or non-evaluable for each drug tested). Patients with an informative tumorogram will receive one of the recommended treatments (line N+1) in the event of tumor progression, administered according to standard procedures and validated at medical meetings specific to each center, and their fate will be monitored.
- Detailed Description
A biopsy of a breast tumor lesion will be performed and transferred to the LIP laboratory at the Institut Curie (Laboratoire d'Investigation Préclinique, Département de Recherche Translationnelle) for processing to establish avatars (patient-derived organoids -PDO).
Step 1: Establishment of avatar (PDO): follow-up of line N (standard care) when the tumorogram is established, then follow-up of standard line N+1.
* The patient will then be treated (line N) as part of standard care while awaiting the result of the tumorogram.
* A drug screening will be carried out on the PDO (\~5-10 drugs/patient), which will be progressive and adapted to the clinical context (including treatment history), including drugs used in standard care (cf. list in Table 1).
* A personalized tumorogram for each patient will be provided, based on the results of the drug screening (= tumor predicted as sensitive, intermediate, resistant or non-evaluable for each drug tested).
* A multidisciplinary committee will be set up for this study, which will meet regularly (\~1 time per week) to discuss patients included in the study, obtaining PDOs, drugs to be prioritized in the screening, results of the drug screening and personalized tumorograms. The committee will include at least one oncologist and one biologist from the laboratory.
* The multidisciplinary committee will make a therapeutic recommendation based on the personalized tumorogram, which may include several drugs considered sensitive to the tumour
* A tumorogram will be considered as informative if it proposes at least one chemotherapy molecule considered as sensitive in the PDO model.
* Patients whose PDO could not be obtained, or whose tumorogram was not informative, will receive standard treatment.
Step 2: informative tumorogram: follow-up of experimental line N+1 Patients with an informative tumorogram will receive one of the recommended treatments (line N+1) in the event of tumor progression, administered according to standard procedures and validated at medical meetings specific to each center, and their fate will be monitored.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 110
- Patient over 18 years of age
- Advanced breast cancer
- Triple-negative phenotype (HR-/HER2-) or HR+/HER2- after hormone resistance (progression after treatment with hormone therapy + CDK4/6 inhibitor)
- Tumor measurable according to RECISTv1.1 criteria, accessible to biopsy
- Performans Status 0-1
- More than 3 lines of chemotherapy in the advanced setting (excluding hormone therapy/CDK4/6 inhibitor)
- Progressive brain metastases
- Leptomeningeal metastasis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Line N in step 1 Biopsy Step 1: follow-up of line N (standard care) when the tumorogram is established. Intervention is the biopsy performed before start of treatment in line N. Standard of Care treatment Line N+1 in step 2 Biopsy Step 2: in case of informative tumorogram: follow-up of experimental line N+1. If tumorogram is informative on organoid issued from biospy, a specific standard of Care treatment will be recommanded.
- Primary Outcome Measures
Name Time Method Tumor response rate 6 months Evaluation in the cohort of patients treated according to the informative tumorogram: tumor response rate within 6 months of the start of this treatment.
Tumor response is defined as partial or complete response, assessed based on radiological criteria (RECIST v1.1) or clinical criteria where applicable.
- Secondary Outcome Measures
Name Time Method Comparison of response rate between both the arms 6 months Comparison of response rate and PFSn+1 (recommended treatment) with response rate and PFSn+1 of patients who did not have an established tumorogram;
Organoid cultures achievement 6 months Percentage of achievement of a PDO
Overall survival up to 18 months Comparison of overall survival (OSn+1, defined as the time between the start of treatment on line n+1 and death) between patients treated according to the tumorogram and patients without a tumorogram and treated according to the guidelines.
Tumorograms performance 6 months Percentage of informative tumorograms versus number of tumorograms returned
Trial Locations
- Locations (2)
Institut Curie
🇫🇷Saint-Cloud, France
Hôpital Saint-Louis - AP-HP Senopole
🇫🇷Paris, France