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

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).

Study Overview

• Status: Completed
• Conditions: Women With BRCA1 Germline Deleterious Mutation
• Intervention / Treatment: Procedure: Blood sampling

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69273
    • Centre Leon Berard
  • Paris, France, 75005
    • Institut Curie
  • Saint-cloud, France, 92210
    • Hôpital René Huguenin - Institut Curie
  • Villejuif, France, 94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient with no evidence of any invasive tumor mass at inclusion (clinical and, if any, radiological exams)
2. Carriers of known germline BRCA1 deleterious mutation (a personal history of cancer is NOT mandatory).
3. Age ≥ 30 years for patient with personal previous history of cancer
4. Age ≥ 40 years for patient without personal previous history of cancer
5. Patient who a follow-up visit is scheduled in the including center at least once a year
6. Patient having health care insurance
7. Signed informed consent by patient

Exclusion Criteria:

1. Patient presenting with invasive tumor masses (e.g. stage IV cancer or localized cancer not yet surgically removed)
2. Carriers of germline BRCA1 variant of unknown significance
3. Carriers of germline BRCA2 deleterious mutation or variant
4. Individuals with a low risk of BRCA1-related tumor growth, i.e. women who underwent prophylactic bilateral mastectomy AND adnexectomy.
5. Any medical or other condition that in the Investigator's opinion rendered the patient unsuitable for this study
6. Patient deprived from ability to decide on her own.
7. Patient unable to have a regular follow up for geographical, social or psychological reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Blood sampling	Procedure: Blood sampling; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institut Curie
• Investigators: Principal Investigator: Jean-Yves PIERGA, DR, Institut Curie

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): December 29, 2021
• Study Completion (Actual): December 29, 2021

Study Registration Dates

• First Submitted: November 16, 2015
• First Submitted That Met QC Criteria: November 16, 2015
• First Posted (Estimated): November 18, 2015

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Circulating tumor DNA; Circulating tumor cells; BRCA1 mutation
• Other Study ID Numbers: IC 2014-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.
• IPD Sharing Time Frame: Data requests can be submitted starting 9 months after last 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 research, 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: SAP