Circulating Tumor DNA After Neoadjuvant Chemotherapy

Official title

Detection of Circulating Tumoral DNA Mutations (Sequential Assessment) Following Neoadjuvant Chemotherapy for Breast Cancer: Clinical Validity (ALIENOR Study)

Overview

Trial assessing the prognostic value of ctDNA mutations from samples taken sequentially in patients with invasive breast cancer initially treated with neoadjuvant chemotherapy and whose tumor is not in complete histological response.

Detailed description

Patients with an invasive breast cancer on neoadjuvant chemotherapy (with the exception of cT2cN0 tumors) are preselected before the surgical procedure. They are definitely included during the post-surgery visit following the analysis of the surgical specimen (only patients whose tumor did not achieve a complete pathological response are included).

Sequential plasma samples for ctDNA mutations analysis will be taken during the post-surgery visit (within 2-5 weeks after surgery) and every 6 months (+/- 1 month) thereafter for 5 years.

In case of relapse patients will be proposed to participate to an optional research program with a blood test for ctDNA assessment and biopsies from a metastasis (when these biopsies are clinically indicated).

Interventions

• Other Follow-up after neoadjuvant chemotherapy
  Sequential plasma samples for ctDNA mutations analysis will be taken during the post-surgery visit (within 2-5 weeks after surgery) and every 6 months (+/- 1 month) thereafter for 5 years. In case of relapse patients will be proposed to participate to an optional research program with a blood test for ctDNA assessment and biopsies from a metastasis (when these biopsies are clinically indicated). Next Generation Sequencing (NGS) analysis will be performed on post-neoadjuvant chemotherapy residual

Primary outcome measures

• Prognostic value of the presence of ctDNA mutation(s) measured by dPCR on recurrence-free interval (RFI) at 3 years. [Time frame: 3 years]

Secondary outcome measures (8)

• Prognostic value of the presence of ctDNA mutation(s) on overall survival (OS) at 3 years. [Time frame: 3 years]
• Prognostic value of the presence of ctDNA mutation(s) on distant-metastasis-free interval (DRFI) at 3 years. [Time frame: 3 years]
• Prognostic value of the presence of ctDNA mutation(s) on OS at 5 years. [Time frame: 5 years]
• Prognostic value of the presence of ctDNA mutation(s) on DRFI at 5 years. [Time frame: 5 years]
• Prognostic value of the presence of ctDNA mutation(s) on a single sample assessment after surgery (measured by dPCR) on RFI at 3 years. [Time frame: 3 years]
• Prognostic value of the presence of ctDNA mutation(s) on a single sample assessment after surgery (measured by dPCR) on DRFI at 3 years. [Time frame: 3 years]
• Prognostic value of the presence of ctDNA mutation(s) on a single sample assessment after surgery (measured by dPCR) on RFI at 5 years. [Time frame: 5 years]
• Prognostic value of the presence of ctDNA mutation(s) on a single sample assessment after surgery (measured by dPCR) on DRFIat 5 years. [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years (no age limit).
• Women or men.
• Invasive breast cancer proven histologically at diagnosis (before neoadjuvant chemotherapy):

• Locally advanced tumor known to be inoperable from the start:

• cT4a, b, c, d whatever the cN
• or cN2 or cN3 whatever the cT.
• Operable tumors:

• cT2cN1 or cT3cN0 or cT3N1,
• or cT2cN0 for which ganglionic invasion has been proven by cytology or histology.
• Lack of clinically or radiologically detectable metastases in the initial diagnosis before the neoadjuvant chemotherapy (M0).
• Unilateral or bilateral breast cancer. Multifocality is accepted.
• Patients who received 6 to 8 cycles of neoadjuvant chemotherapy.
• Preoperative radiation therapy allowed.
• Breast surgery performed and pathology report of a non-complete histological response (i.e. all the different results of ypT0 /is ypN0).
• Signed informed consent.
• Patients affiliated to a French social security scheme in accordance with Article 1121-11 of the French Code of Public Health.
• Possible inclusion in another interventional research (surgical, radiotherapy or drug study).

Exclusion criteria

• cT2cN0 tumor without cytological or histological lymph node involvement.
• Progression during neoadjuvant chemotherapy.
• Exclusive neoadjuvant hormone therapy.
• Complete blood transfusion within 120 days prior to 1st sampling.
• History of invasive cancer regardless of the time elapsed since the diagnosis of this cancer, including a history of contralateral invasive breast cancer. However, patients who have been treated for in situ breast cancer, basocellular skin cancer or cervical cancer treated in situ are eligible.
• Patient unable to follow and comply with research procedures for geographical, social or psychological reasons.
• Patient deprived of liberty or subject to a legal protection measure.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

France · 1 center

• Institut Bergonie — Bordeaux

Identifiers

NCT: NCT03357120 · IB 2017-02 · ID-RCB number : 2017-A00939-44

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗