Biomarkers in Patients With Metastatic Breast Cancer (BIOPEACE)

Tunisian Association for Immuno-oncology Research

Status: Not yet enrolling

Conditions: Identify the Number of Eligible Patients for Immunotherapy According to the Epidemiological and Biological Profile in Tunisia

Treatments: Diagnostic Test: identify biomarkers

Study type: Observational

Funder types: Other

Identifiers

NCT05871788

ECOCS2020-01

Details and patient eligibility

About

In order to allow Tunisian patients with breast cancer to access immunotherapies, and innovative treatments to extend life expectancy of patients with breast cancer with a poor prognosis, it is important to study the epidemiological profile of Tunisian cancers breast, in terms of PD-L1 expression, tumor mutational burden (TMB), microsatellite instability status (MSI) and rate of TILs, in metastatic and locally advanced cases, in Tunis, over a one-year follow-up period.

It is also important to study other inflammatory and tumor biomarkers which would have a prognostic or even therapeutic value:

• serum dosage of LDH (lactate dehydrogenase)
• IL-6 (interleukin 6)
• CRP (C-reactive protein)
• absolute count of lymphocytes (CLA) and eosinophils
• quantification of circulating tumor DNA before treatment and under treatment. The primary objective id to identify the epidemiological profile of the biological signature (PD-L1 / TMB / MSI/HRD/ TILs) of patients with locally advanced or metastatic breast carcinoma before and during the systemic treatment.

Full description

Procedure:

1. Verification of the inclusion / non-inclusion criteria

2. Signing the consent form

3. Surgical, Medical and family history, ongoing treatments

4. Clinical Examination1

5. Radiological examinations 2

6. TNM Classification (Appendix 3)

7. Standard biochemical assessment 3

8. Inflammatory assessment (CRP, LDH, IL6)

9. Hematological assessment (NFS, platelets)

10. Tumor markers (ACE, CA15-3)

11. Histological and molecular examination 4:

    • Expression PD-L1 by IHC (Immuno-Histochemistry)
    • TILs by IHC
    • • MSI status: MMR * proteins (Mismatch Repair Protein) (Appendix 4) by NGS via TruSight™ Oncology 500 Kit (Illumina) , if PD-L1>1%
    • Score HRD : by NGS via TruSight™ Oncology 500 Kit (Illumina) , if PD-L1>1%
    • TMB mutational burden by next generation sequencing "Next Generation Sequencing" (NGS) via TruSight™ Oncology 500 Kit (Illumina) if PD-L1>1%
    • tDNA by digital PCR

12. Radiological evaluation5

13. Indication of surgery? (if yes type of surgery to be specified)

14. Evaluation of adverse events / effects: Tolerance of the previous treatment

15. Completion the source documents and the eCRF

    Clinical Exam1:

    • General State according to the WHO classification or according to the Karnowsky Index
    • Breast examination: inspection (symmetry, appearance of the skin), palpation (size of the tumor, presence of mammary discharge).
    • Examination of the axillary and supraclavicular lymph node areas
    • Abdominal examination
    • Pulmonary auscultation
    • Skeleton examination Radiological examination2:
    • Mammography and echo-mammary
    • Thoraco-abdomino-pelvic CT scan
    • Bone scintigraphy
    • Cardiac ultrasound

    Standard biochemical balance3:

    Blood group, creatininemia, blood ionogram, calcemia, glycemia, bilirubin, transaminases, gamma-GT, alkaline phosphatases, total cholesterol, triglycerides, uric acid, albuminemia.

    Histological examination4:

    • Biopsy with part number assigned by the laboratory, name of the laboratory
    • Histological type
    • Grade of Scarff-Bloom and Richardson (SBR)
    • Estrogen receptors, progesterone receptors
    • Her2Neu
    • Ki67
    • PD-L1
    • TILs
    • MMR

    Molecular Examination4:

    • MSI status by pentaplex PCR and capillary electrophoresis by NGS platform via the TruSight™ kit Oncology 500 (Illumina)

    • HRD Score by NGS platform via the TruSight™ kit Oncology 500 (Illumina)

    • Mutational burden TMB by NGS platform via the TruSight™ kit Oncology 500 (Illumina)

    • Circulating tumor DNA by digital PCR Radiological assessment5:

    • If the stage is locally advanced (appendix 3): Breast ultrasound +/- Mammography +/- Breast MRI

    • If metastatic stage: Thoraco-abdomino-pelvic CT scan 12 | 27 Visit details

      • Initial visit D0 (V1)

      • Signature of informed consent form
      • Verification of inclusion / non-inclusion criteria
      • Medical, surgical and family history
      • Current treatments
      • Clinical examination1
      • Radiological examinations2
      • TNM classification
      • Standard biochemical assessment3
      • Inflammatory assessment (CRP, LDH, IL6)
      • Hematological assessment (NFS, platelets)
      • Tumor markers (ACE, CA15-3)
      • Histological examination with immunohistochemistry and molecular4:

    • Biopsy with part number assigned by the lab, name of the lab

    • Histological type

    • SBR grade

    • Estrogen receptors, progesterone receptors

    • Her2Neu

    • Ki67

    • PD-L1

    • TILs

    • MMR

    • MSI

    • HRD

    • TMB mutational charge

    • ctDNA o Completion of source documents and eCRF

      • Visit after 3 chemotherapy treatment cycles (V2)

        • Current treatments
        • Clinical examination1
        • Hematological assessment (NFS, platelets)
        • Tumor markers (ACE, CA15-3)
        • Radiological assessment5
        • Evaluation of adverse events / effects: Tolerance of the previous treatment
        • Completion of source documents and eCRF

      • Assessment visit (V3) o Current treatments

        o Clinical examination1

        • TNM classification
        • Inflammatory assessment (CRP, LDH, IL6)
        • Hematological assessment (NFS, platelets)
        • Tumor markers (ACE, CA15-3)
        • Histological examination with immunohistochemistry and molecular4:

    • Biopsy with part number assigned by the lab, name of the lab

    • Histological type

    • SBR grade 13 | 27

    • Estrogen receptors, progesterone receptors

    • Her2Neu

    • Ki67

    • PD-L1

    • TILs

    • ctDNA

      o Radiological assessment5

      o Assessment of adverse events / effects

      o Fill in the source files and the eCRF

      • Follow-up visit at 3 months (V4)

        o Current treatments

        o Clinical examination1

        o Tumor markers (ACE, CA15-3)

        o Radiological examinations2

        o Evaluation of adverse events / effects

        • Completion of source documents and eCRF

      • Follow-up visit at 6 months (V5) o Current treatments o Clinical examination1 o Tumor markers (ACE, CA15-3)

        • Radiological examinations2
        • Evaluation of adverse events / effects
        • Completion of source documents and eCRF

Enrollment: 1,600 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥ 18 years old.
• Signed informed consent
• Histological evidence of breast carcinoma.
• Locally advanced (stage III inoperable) or metastatic (stage IV) carcinoma, the metastases of which have been diagnosed straight away or after adjuvant or neoadjuvant treatment.
• No treatment for metastatic disease.
• Metastatic disease: histological evidence of metastasis
• Patients who will receive systemic treatment (chemotherapy, targeted therapy, hormone therapy)
• Life expectancy greater than 3 months

Exclusion criteria

• Non-epithelial breast cancer

• Non-biopsiable metastases

• Patients who have received before systemic treatment for metastatic disease (chemotherapy, targeted therapy, hormone therapy)

• Patients with a contraindication to chemotherapy, and / or hormone therapy, and

  / or targeted therapy.

• Foreign patients