Efficacy of Personalized Tumorogram-based Therapy in Cancer Established From Patient-derived Organoid (AVATAR)

Institut Curie

Status: Enrolling

Conditions: Metastatic Breast Cancer

Treatments: Procedure: Biopsy

Study type: Interventional

Funder types: Other

Identifiers

NCT06459791

IC 2023-08

Details and patient eligibility

About

A biopsy of a tumor lesion (breast or other localisation) 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.

Full description

A biopsy of a tumor lesion (breast or other localisation) 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.

Enrollment: 110 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patient over 18 years of age
2. Advanced breast cancer
3. Triple-negative phenotype (HR-/HER2-) or HR+/HER2- after hormone resistance (progression after treatment with hormone therapy + CDK4/6 inhibitor)
4. Tumor measurable according to RECISTv1.1 criteria, accessible to biopsy
5. Performans Status 0-1

Exclusion criteria

1. More than 3 lines of chemotherapy in the advanced setting (excluding hormone therapy/CDK4/6 inhibitor)
2. Progressive brain metastases
3. Leptomeningeal metastasis

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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110 participants in 2 patient groups

Line N in step 1

Other group

Description:

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

Treatment:

Procedure: Biopsy

Line N+1 in step 2

Experimental group

Description:

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.

Treatment:

Procedure: Biopsy