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

Metastatic Breast Cancer Clinical Trial

— AVATAR  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06459791
• Other study ID #: IC 2023-08_AVATAR
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 15, 2024
• Est. completion date: September 30, 2028

Study information

• Verified date: May 2024
• Source: Institut Curie
• Contact: Luc CABEL, MD
• Phone: +33 1 56 24 55 00
• Email: drci.promotion[@]curie.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 110
• Est. completion date: September 30, 2028
• Est. primary completion date: December 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Procedure:
• Biopsy
The recommandation done based on informative tumorogram is up to study investigator

Locations

Country	Name	City	State
France	Hôpital Saint-Louis - AP-HP Senopole	Paris
France	Institut Curie	Paris
France	Institut Curie	Saint-Cloud

Sponsors (1)

Lead Sponsor	Collaborator
Institut Curie

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Organoid cultures achievement	Percentage of achievement of a PDO	6 months
Secondary	Tumorograms performance	Percentage of informative tumorograms versus number of tumorograms returned	6 months
Secondary	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