Validation of Molecular Diagnostic Assays to Detect Cancer Biomarkers in Blood & Primary Tumor in ER+/HER2- MBC

Study Overview
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Brief Summary
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Conventional biopsy and surgical tumor resection are invasive procedures that capture only one instance of the progression of the tumor. However, the genome of tumor is not static, but it is constantly altered during treatment. Liquid biopsy is a non-invasive approach based on the extraction of information through peripheral blood analysis. It makes it possible to characterize the development of a solid tumor in real time, through detailed molecular analysis of circulating genetic material in peripheral blood.

Detailed Description
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Conventional biopsy and surgical tumor resection are invasive procedures that capture only one instance of the progression of the tumor. However, the genome of tumor is not static, but it is constantly altered during treatment. Liquid biopsy is a non-invasive approach based on the extraction of information through peripheral blood analysis. It makes it possible to characterize the development of a solid tumor in real time, through detailed molecular analysis of circulating genetic material in peripheral blood. Study procedure: Initial Visit (V0-Baseline): For the purposes of the study the following information will be collected: the demographics, medical and social history, the characteristics of the disease (stage, molecular characterization e.t.c) and the treatment regimen that is followed. As part of the visit, 20 mL of peripheral blood will be drawn prior to their treatment according to physician's suggestion as per common clinical practice. Blood samples will be then sent to ACTC laboratory for plasma/CTC isolation, DNA and RNA extraction and subsequent test for biomarkers. Primary tumor tissue samples will be also collected Follow-up visit (V1): Response to treatment by RECIST based on restaging CTs/MRIs will be documented during this visit, which will take place 3 months after treatment initiation. As part of the visit, 20 mL of peripheral blood will be drawn. Blood samples will be then sent to laboratory for plasma/CTC isolation, DNA and RNA extraction and subsequent test for biomarkers. Survival status and clinical response (CR, PR, SD, PD) will be also documented.

Official Title
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A Clinical Performance Study to Validate the Use of Novel Molecular Diagnostic Assays for the Detection of Cancer Biomarkers in Peripheral Blood and Primary Tumor Tissue Samples of Patients With Metastatic ER+/HER2- Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Diagnostic Test: PIK3CA kit


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female aged ≥ 18 years of age. Histological confirmed ER+/HER2- metastatic Breast Cancer prior to beginning a treatment Life expectancy permits participation to the study. Available tumor tissue sample for molecular analysis. Signed informed consent form. Exclusion Criteria: Female younger than 18 years old. History of another malignancy within 3 years or current 2nd primary malignancy. Patients that have not signed the informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Metastatic Breast Cancer<br>The study population are subjects with a confirmed diagnosis of ER+/HER2 metastatic Breast Cancer patient before the treatment initiation. The selected inclusion/exclusion criteria have been set to include in the performance study appropriate population of interest, as broad as possible, but to exclude these subjects that have another current malignancy or any history of recent malignancy within 3 years. | Diagnostic Test: PIK3CA kit<br>* Prospective investigation of clinical samples for evaluation of IVD clinical performance<br>|
| Healthy volunteers<br>In case of healthy volunteers only peripheral blood samples will be collected. | Diagnostic Test: PIK3CA kit<br>* Prospective investigation of clinical samples for evaluation of IVD clinical performance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical performance of PIK3CA kit in CTCs, plasma and tumor tissue samples of metastatic breast cancer patients | The performance of PIK3CA kit on detecting mutations in CTCs samples of metastatic breast cancer patients will be assessed via Sensitivity, Specificity, Positive and Negative Predictive Values, Positive and Negative Likelihood Ratios, Accuracy and Diagnostic Odds Ratio. The point of primary evaluation in CTCs samples will be at baseline and droplet digital PCR will be used as reference method. The performance of PIK3CA kit on detecting mutations in plasma-ctDNA, and tumor tissue samples of metastatic breast cancer patients will be assessed via Sensitivity, Specificity Positive and Negative Predictive Values, Positive and Negative Likelihood Ratios, Accuracy and Diagnostic Odds Ratio. The point of primary evaluation in plasma-ctDNA and tumor tissue samples will be at baseline and therascreen PIK3CA RGQ PCR Kit will be used as reference method. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - To study the PIK3CA Mutation Status before and after treatment of metastatic breast cancer patients using PIK3CA kit. | Presence of PIK3CA mutations at a second visit following to baseline of metastatic breast cancer patients using the PIK3CA kit. | 24 months | 
| - To assess the PIK3CA Mutation Status before treatment vs treatment response of metastatic breast cancer patients using PIK3CA kit. | Association of PIK3CA mutations presence at baseline with clinical response to treatment (CR, PR, SD, PD) of metastatic breast cancer patients using PIK3CA kit. | 24 months | 
| - To correlate patients' survival status with PIK3CA mutations at baseline | Metastatic breast cancer patients' survival status by presence of PIK3CA mutations at baseline. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liquid biopsy, CTC, Plasma, PIK3CA