Evaluation of an Automated System to Culture Metastatic Patient Circulating Tumor Cells in Embryonated Chicken Eggs (in Ovo Culture)

Study Overview
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Brief Summary
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A variety of in vivo experimental models have been established for the studies of human cancer using both cancer cell lines and patient-derived xenografts (PDXs). In order to meet the aspiration of precision medicine, the in vivo murine models have been widely adopted. However, common constraints such as high cost, long duration of experiments, and low engraftment efficiency remained to be resolved. The chick embryo chorioallantoic membrane (CAM) is an alternative model to overcome some of these limitations. The chick CAM is shown to be a robust model for both the inoculation of cell lines and grafting of patient tumors for drug therapy evaluations and target genes/pathways analysis. The start-up INOVOTION has developed a unique, highly sensitive and reproducible CAM assay to graft human cancer cells/tumors in the chicken egg environment. INOVOTION's technology was validated for over 55 human tumor cell lines, including carcinomas, gliomas and melanomas, as well as over 30 reference drugs currently on the market. At INOVOTION, the graft of human cancer cells on the chicken CAM is currently conducted manually. To scale-up, the process was recently automated. The automation performance was assessed on cancer cells lines. The objective of this study is to demonstrate that the automation of the INOVOTION process enables tumors' proliferation using patient samples (from tumor samples or circulating tumor cells) as grafting material.

Official Title
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Evaluation of an Automated System to Culture Metastatic Patient Circulating Tumor Cells in Embryonated Chicken Eggs (in Ovo Culture)

Conditions
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Cancer Metastatic, Prostate Cancer, Breast Cancer, Lung Cancer, Ovarian Cancer, Gastric Cancer

Intervention / Treatment
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* Procedure: Patient sampling.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for all cohorts * : Age > 18 Signed consent Inclusion criteria for the Prostate cohort: prostate adenocarcinoma histologically proven metastatic situation at least 2 metastatic sites Evolutionary disease that requires a new treatment Inclusion criteria for the Breast cohort: HER2+ or RH+ breast adenocarcinoma histologically proven metastatic situation at least 2 metastatic sites Evolutionary disease that requires a new treatment Inclusion criteria for the Lung cohort: Non Small Lung cancer histologically proven metastatic situation at least 2 metastatic sites Evolutionary disease that requires a new treatment Inclusion criteria for Ovarian cohort: Ovarian cancer histologically proven Presence of peritoneal carcinomatosis (stage IIIC or IV); with or without presence of peritoneal fluid Inclusion criteria for Colo-Rectal cohort: Colo-rectal cancer histologically proven Presence of peritoneal carcinomatosis, with or without presence of peritoneal fluid Evolutionary disease that requires a new treatment Inclusion criteria for Gastric cohort: Gastric cancer histologically proven Presence of peritoneal carcinomatosis, with or without presence of peritoneal fluid Exclusion Criteria for all cohorts * : Weight <50kg Parallel participation in a doubled blinded study Brain or ganglionary metastasis only

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 6 cohort<br>Prostate Cohorte : Castrate resistant metastatic prostate cancer patient Breast cohort : HER2+ ou RH+ metastatic breast cancer patient Lung cohort : Non-small cell lung metastatic lung cancer patient Ovarian cohort : Ovarian cancer with peritoneal carcinomatosis Colorectal cohort : Colorectal cancer with peritoneal carcinomatosis Gastric cancer : Gastric cancer with peritoneal carcinomatosis | Procedure: Patient sampling.<br>* One or several bio-specimens will be sampled depending on the cohort : Blood (40 ml) Pleural Fluid (40 ml) Peritoneal liquid (40 ml) Solid tumors<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The main primary endpoint will be reached, if the xenograft rate using patients' samples is ≥ 50% with the INOVOTION automated process. | A xenograft will be considered successful if proliferating human material is found in at least one of the egg engrafted with the patient sample (one patient sample being able to be used to engraft several eggs). Success = at least one successful xenograft on all engrafted eggs with a patient sample Failed: 0 successful xenograft on all engrafted eggs with a patient sample | The sample outcome will be measured 19 days after egg engraftment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of the xenograft rate per patient sub-population and per cohort (patient blood CTC, pleural fluid, peritoneal fluid, tumor pieces) | A xenograft will be considered successful if proliferating human material is found in at least one of the egg engrafted with the patient sample (one patient sample being able to be used to engraft several eggs). Success = at least one successful xenograft on all engrafted eggs with a patient sample Failed: 0 successful xenograft on all engrafted eggs with a patient sample | The sample outcome will be measured 19 days after egg engraftment | 
| Biological characteristics of the obtained xenografts (per cohort) | NGS xenograft analysis | One to two months after egg engrafting | 
| Study of xenograft biological responses under different cancer drug treatment (per cohort) | biological responses analysis. | 19 days after egg engraftment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chick embryo chorioallantoic membrane, in ovo technology, cancer, Metastatic cancer, CTC, process automation