Circulating Tumor DNA and Follow-up of BRCA1 Mutation Carriers (CirCa 01)

Study Overview
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Brief Summary
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BRCA1 carriers who are at high risk of developing either a relapse and/or a new cancer growth will be included. These patients will be followed up during 30 months (2,5 years) with mutated TP53 mutation detection or during 42 months (3,5 years) with mutated TP53 mutation detection and circulating tumor cells detection (CTC) performed at each hospital visit (for technical reason only patients included at Institut Curie will be proposed to participate to the CTC substudy).

Official Title
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Circulating Tumor DNA and Follow-up of BRCA1 Mutation Carriers (CirCa 01)

Conditions
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Women With BRCA1 Germline Deleterious Mutation

Intervention / Treatment
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* Procedure: Blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with no evidence of any invasive tumor mass at inclusion (clinical and, if any, radiological exams) Carriers of known germline BRCA1 deleterious mutation (a personal history of cancer is NOT mandatory). Age ≥ 30 years for patient with personal previous history of cancer Age ≥ 40 years for patient without personal previous history of cancer Patient who a follow-up visit is scheduled in the including center at least once a year Patient having health care insurance Signed informed consent by patient Exclusion Criteria: Patient presenting with invasive tumor masses (e.g. stage IV cancer or localized cancer not yet surgically removed) Carriers of germline BRCA1 variant of unknown significance Carriers of germline BRCA2 deleterious mutation or variant Individuals with a low risk of BRCA1-related tumor growth, i.e. women who underwent prophylactic bilateral mastectomy AND adnexectomy. Any medical or other condition that in the Investigator's opinion rendered the patient unsuitable for this study Patient deprived from ability to decide on her own. Patient unable to have a regular follow up for geographical, social or psychological reasons.

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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Female

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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Blood sampling<br> | Procedure: Blood sampling<br>* Patients will have a blood draw at each visit to the hospital, with a maximum of 1 blood draw every 3 months, in absence of any abnormal clinical/radiological exam with a maximum of 1 blood draw every week, in case of abnormal clinical/radiological exam that requires further investigation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of plasma TP53 mutation detection as a test to detect any tumor growth (relapse and/or new tumor) during the follow-up of women known to carry BRCA1 germline mutation | Sensitivity = % of patients with detectable levels of mutated TP53 ctDNA among those who experience a new tumor growth (relapse and/or new tumor). | Up to 42 months | 
| Specificity of plasma TP53 mutation detection as a test to detect any tumor growth (relapse and/or new tumor) during the follow-up of women known to carry BRCA1 germline mutation | Specificity = % of patients with undetectable levels of mutated TP53 ctDNA among those who don't experience a new tumor growth (diagnosed within 6 months after the blood draw). | Up to 42 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive predictive value for mutated TP53 ctDNA | Positive predictive value = Probability of having a tumor growth (relapse and/or new tumor) when mutated TP53 ctDNA is detectable. | Up to 42 months | 
| Negative predictive value for mutated TP53 ctDNA | Negative predictive value = Probability of being without tumor growth when mutated TP53 ctDNA is not detectable. | Up to 42 months | 
| Sensitivity of circulating tumor cells detection as a test to detect any tumor growth (relapse and/or new tumor) during the follow-up of women known to carry BRCA1 germline mutation | Sensitivity = % of patients with detectable levels of circulating tumor cells among those who experience a new tumor growth (relapse and/or new tumor). | Up to 42 months | 
| Specificity of circulating tumor cells detection as a test to detect any tumor growth (relapse and/or new tumor) during the follow-up of women known to carry BRCA1 germline mutation | Specificity = % of patients with undetectable levels of circulating tumor cells among those who don't experience a new tumor growth (diagnosed within 6 months after the blood draw). | Up to 42 months | 
| Positive predictive value for circulating tumor cells | Positive predictive value = Probability of having a tumor growth (relapse and/or new tumor) when circulating tumor cells is detectable. | Up to 42 months | 
| Negative predictive value for circulating tumor cells | Negative predictive value = Probability of being without tumor growth when circulating tumor cells is not detectable. | Up to 42 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Circulating tumor DNA, BRCA1 mutation, Circulating tumor cells