Breast CancerCICLADESNCT03318263
CIrCuLAting Dna ESr1 Gene Mutations Analysis
A study testing next-generation sequencing (NGS) in people with Breast Cancer, run by Institut de Cancérologie de Lorraine at 10 sites in France.
Trial summary
The estrogen-dependent nature of breast cancer was first reported in 1896 with the publication of George Beatson's observations on the regression of breast cancer following oophorectomy. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- next-generation sequencing (NGS)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 146 participants
- Where
- 10 sitesFrance
- Study dates
- 7 Dec 2017to 22 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patient aged 18 and older
- Histologically confirmed estrogen-receptor-positive, HER2-negative breast cancer
- Proven metastatic (AJCC stage IV) or loco-regionally advanced (AJCC stage III) breast cancer, not amenable to surgery or radiation with curative intent.
- Indication to treat with first-line endocrine therapy for palliative care.
- Patients already receiving first-line endocrine therapy can be enrolled up to 6 weeks after start of endocrine therapy.
- Endocrine therapy can be prescribed in combination with a CDK4/6 inhibitor.
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- One prior regimen of chemotherapy for the treatment of advanced disease is allowed.
- Prior (neo)adjuvant chemotherapy and/or (neo)adjuvant endocrine therapy is/are allowed; patients with recurrence while on adjuvant endocrine therapy can be enrolled.
- Patients who can benefit from an additional blood sample of 10ml. The total volume of each sample meets with the indications of the Order in force establishing the list of researches mentioned in 2 ° of Article L. 1121-1 of the Public Health Code.
- Informed consent explained to, understood by and signed by patient. Patient must be given a copy of informed consent.
- Patients affiliated to a social security scheme or benefit from a social regime
- The prescription of medicinal product(s) is clearly separated from the decision to include the subject in this ISMRC.
Who cannot join
- Pregnant or breast-feeding woman.
- Patient who received any prior systemic hormonal therapy for advanced breast cancer; no more than one prior regimen of chemotherapy for the treatment of advanced disease is allowed.
- Chemotherapy in combination with endocrine therapy.
- Targeted therapy, except CDK 4/6 inhibitor, in combination with endocrine therapy.
- Planned surgery or radiation with curative intent.
- Other active malignancy.
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- Any concurrent severe and/or uncontrolled medical condition(s) which could compromise participation in the study.
- Patient whose general state and / or conditions do not permit the collection of the additional blood sample.
- Patients under guardianship, under curatorship or deprived of liberty.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
France10 sites
Hôpital Claude Bernard
Metz, 57070
CHR Metz-Thionville
Metz, 57085
Centre d'oncologie Gentilly
Nancy
Institut Jean Godinot
Reims, 51100
Polyclinique de Courlancy
Reims, 51100
Centre Henri Becquerel
Rouen, 76038
Polyclinique de l'Orangerie
Strasbourg, 67000
Clinique Saint Anne
Strasbourg, 67085
CHU Strasbourg
Strasbourg, 67091
Institut de cancérologie de Lorraine
Vandœuvre-lès-Nancy, 54509
About this study
Official title: Monitoring of ESR1, PIK3CA and AKT ctDNA Mutations During Real-life Followup of Patients With Metastatic Breast Cancer Treated With Aromatase Inhibitors
The estrogen-dependent nature of breast cancer was first reported in 1896 with the publication of George Beatson's observations on the regression of breast cancer following oophorectomy. Endocrine therapy, targeting ER either directly by selective estrogen receptor modulators (SERMs) and pure antagonists or indirectly by aromatase inhibitors (AIs) that block estrogen production, remains the mainstay of treatment of hormone-sensitive breast cancer in the adjuvant and metastatic settings.
Intrinsic (de novo) and acquired endocrine resistance constitutes an important clinical challenge in the treatment of breast cancer and multiple mechanisms are suspected to underlie the emergence of endocrine resistance.
Read more
The role of the estrogen receptor (ER), encoded by the ESR1 gene, in normal mammary gland development and the progression of breast cancer is well established. ESR1 mutations, occurring in 10 to 30% of ER-positive metastatic breast cancer resistant to AIs, lead to ligand-independent activation of the ER.
For patients treated with AIs, monitoring of circulating tumour DNA (ctDNA) for ESR1, PIK3CA and AKT1 mutations could permit early detection of resistance to AIs as recently reported during 2016 American Society of Clinical Oncology (ASCO) meeting.
- Conditions
- Breast Cancer
- Being tested
- next-generation sequencing (NGS)
- Keywords
- Estrogen-receptor-positive breast cancer, aromatase inhibitor,, ESR1,, PIK3CA, AKT, endocrine resistance, circulating tumor DNA
- Medical subject headings
- Breast Neoplasms, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
next-generation sequencing (NGS)Diagnostic test
ESR1, PI3KCA and AKT extensive exon sequencing will be performed using NGS (Miseq Illumina) at the Biopathology department, Institut de Cancérologie de Lorraine (ISO15189 certified lab). Samples taken at baseline (t0), at progression (tp) and 3 months before progression (tp-3) will be systematically analyzed. The intermediate samples will be stored and kept for additional studies. Follow up assessment will be performed according to prescriber's directions.
| Study group | Role | What they receive |
|---|---|---|
| experimental | Other | Not described Receives: Diagnostic Test: next-generation sequencing (NGS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
incidence of ESR1 mutations
Measured: 1 day
Secondary outcomes (5)
incidence of PIK3CA and AKT1 mutations
Measured: 1 day
prevalence of ESR1, PIK3CA and AKT1 mutations in patients with and without endocrine resistance at enrolment
Measured: 1 day
prevalence of ESR1, PIK3CA and AKT1 mutations in patients according to mono vs combo therapy.
Measured: 1 day
prevalence of mutations of other genes of interest included in the panel from the start of treatment to progression or end of follow-up
Measured: 1 day
ESR1, PIK3CA and AKT1 mutations predictor of progression free survival
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2017
- Study start7 Dec 2017
- Primary completion22 Dec 2022
- Study completion22 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 146 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut de Cancérologie de Lorraine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- MASSARD VINCENT, MD, Principal investigator, Institut de Cancérologie de Lorraine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03318263
- Sponsor's protocol ID
- 2017-A01767-46
- Acronym
- CICLADES
- Status last verified
- Aug 2023
- First submitted
- 18 Oct 2017
- Last updated
- 4 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monitoring of ESR1, PIK3CA and AKT ctDNA Mutations During Real-life Followup of Patients With Metastatic Breast Cancer Treated With Aromatase Inhibitors
- ClinicalTrials.gov ID
- NCT03318263
- Acronym / sponsor ID
- CICLADES / 2017-A01767-46
- Conditions
- Breast Cancer
- Keywords
- Estrogen-receptor-positive breast cancer, aromatase inhibitor,, ESR1,, PIK3CA, AKT, endocrine resistance, circulating tumor DNA
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 146 participants (actual)
- Lead sponsor
- Institut de Cancérologie de LorraineUniversity, hospital or other
- Study start
- 7 Dec 2017 (actual)
- Primary completion
- 22 Dec 2022 (actual)
- Study completion
- 22 Dec 2022 (actual)
- First posted
- 23 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The estrogen-dependent nature of breast cancer was first reported in 1896 with the publication of George Beatson's observations on the regression of breast cancer following oophorectomy. Endocrine therapy, targeting ER either directly by selective estrogen receptor modulators (SERMs) and pure antagonists or indirectly by aromatase inhibitors (AIs) that block estrogen production, remains the mainstay of treatment of hormone-sensitive breast cancer in the adjuvant and metastatic settings.
Intrinsic (de novo) and acquired endocrine resistance constitutes an important clinical challenge in the treatment of breast cancer and multiple mechanisms are suspected to underlie the emergence of endocrine resistance.
The role of the estrogen receptor (ER), encoded by the ESR1 gene, in normal mammary gland development and the progression of breast cancer is well established. ESR1 mutations, occurring in 10 to 30% of ER-positive metastatic breast cancer resistant to AIs, lead to ligand-independent activation of the ER.
For patients treated with AIs, monitoring of circulating tumour DNA (ctDNA) for ESR1, PIK3CA and AKT1 mutations could permit early detection of resistance to AIs as recently reported during 2016 American Society of Clinical Oncology (ASCO) meeting.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| experimental | Other | Diagnostic Test: next-generation sequencing (NGS) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Female patient aged 18 and older
- Histologically confirmed estrogen-receptor-positive, HER2-negative breast cancer
- Proven metastatic (AJCC stage IV) or loco-regionally advanced (AJCC stage III) breast cancer, not amenable to surgery or radiation with curative intent.
- Indication to treat with first-line endocrine therapy for palliative care.
- Patients who can benefit from an additional blood sample of 10ml. The total volume of each sample meets with the indications of the Order in force establishing the list of researches mentioned in 2 ° of Article L. 1121-1 of the Public Health Code.
Key exclusion criteria (9 listed)
- Pregnant or breast-feeding woman.
- Patient who received any prior systemic hormonal therapy for advanced breast cancer; no more than one prior regimen of chemotherapy for the treatment of advanced disease is allowed.
- Chemotherapy in combination with endocrine therapy.
- Targeted therapy, except CDK 4/6 inhibitor, in combination with endocrine therapy.
- Planned surgery or radiation with curative intent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| next-generation sequencing (NGS)ESR1, PI3KCA and AKT extensive exon sequencing will be performed using NGS (Miseq Illumina) at the Biopathology department, Institut de Cancérologie de Lorraine (ISO15189 certified lab). Samples taken at baseline (t0), at progression (tp) and 3 months before progression (tp-3) will be systematically analyzed. The intermediate samples will be stored and kept for additional studies. Follow up assessment will be performed according to prescriber's directions. | Diagnostic test | experimental |
Primary outcome
incidence of ESR1 mutations
Time frame: 1 day
5 secondary outcomes
incidence of PIK3CA and AKT1 mutations
Time frame: 1 day
prevalence of ESR1, PIK3CA and AKT1 mutations in patients with and without endocrine resistance at enrolment
Time frame: 1 day
prevalence of ESR1, PIK3CA and AKT1 mutations in patients according to mono vs combo therapy.
Time frame: 1 day
prevalence of mutations of other genes of interest included in the panel from the start of treatment to progression or end of follow-up
Time frame: 1 day
ESR1, PIK3CA and AKT1 mutations predictor of progression free survival
Time frame: 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MASSARD VINCENT, MD principal investigator
Institut de Cancérologie de Lorraine
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing next-generation sequencing (NGS) in people with Breast Cancer, run by Institut de Cancérologie de Lorraine at 10 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
incidence of ESR1 mutations (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2023.