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

Efficacy of Personalized Tumorogram-based Therapy in Cancer Established From Patient-derived Biological Avatar: Proof-of-concept Study

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Procedure: Biopsy

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne-Sophie Plissonnier; Phone Number: +33 1 47 11 23 78; Email: anne-sophie.plissonnier@curie.fr
• Study Contact Backup: Name: Luc CABEL, MD; Phone Number: +33 1 56 24 55 00; Email: drci.promotion@curie.fr

Study Locations

• France
  • Paris, France, 75005
    • Recruiting
    • Institut Curie
    • Principal Investigator: LUC CABEL, MD
    • Contact: Luc CABEL, MD
  • Paris, France, 75010
    • Not yet recruiting
    • Hôpital Saint-Louis - AP-HP Senopole
    • Principal Investigator: Delphine COCHEREAU, MD
    • Contact: Delphine COCHEREAU, MD
  • Saint-Cloud, France, 92210
    • Recruiting
    • Institut Curie
    • Contact: Alexandre DE MOURA, MD
    • Principal Investigator: Alexandre DE MOURA, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Line N in step 1; 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	Procedure: Biopsy; The recommandation done based on informative tumorogram is up to study investigator; Other Names: Line N+1 treatment recommandation
Experimental: Line N+1 in step 2; 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.	Procedure: Biopsy; The recommandation done based on informative tumorogram is up to study investigator; Other Names: Line N+1 treatment recommandation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response rate	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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of response rate between both the arms	Comparison of response rate and PFSn+1 (recommended treatment) with response rate and PFSn+1 of patients who did not have an established tumorogram;	6 months
Organoid cultures achievement	Percentage of achievement of a PDO	6 months
Tumorograms performance	Percentage of informative tumorograms versus number of tumorograms returned	6 months
Overall survival	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.	up to 18 months

Collaborators and Investigators

• Sponsor: Institut Curie
• Investigators: Principal Investigator: Luc CABEL, MD, Institut Curie

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2024
• Primary Completion (Estimated): December 15, 2027
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: May 27, 2024
• First Submitted That Met QC Criteria: June 10, 2024
• First Posted (Actual): June 14, 2024

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 27, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: avatar; metastatic breast cancer; Organoid; PDO; tumorogram
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Diagnostic Techniques, Surgical; Biopsy
• Other Study ID Numbers: IC 2023-08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Investigators will share de-identified data sets with interested researchers, educators or clinicians. Materials generated under the project will be disseminated in accrodance with Institut Curie policies.
• IPD Sharing Time Frame: Data requests can be submitted starting 9 months after article publication and will be made accessible for up to 12 months.
• IPD Sharing Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific reserach, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No