Clinical trial NCT05871788: Biomarkers in Patients With Metastatic Breast Cancer
Official title: Biomarkers in Patients With Metastatic Breast Cancer
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Identify the Number of Eligible Patients for Immunotherapy According to the Epidemiological and Biological Profile in Tunisia
Lead sponsor: Tunisian Association for Immuno-oncology Research
Sponsor class: OTHER
First posted: 2023-05-23
Enrollment: 1600
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with metastatic or locally advanced breast cancer in Tunis, Tunisia.

Brief summary: 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: number of eligible patients for immunotherapy
timeFrame: 2023 to 2027
Secondary outcomes:
measure: Relevance of immunotherapy in Tunisia
timeFrame: 2023 to 2027
Other outcomes:
Locations:
Study officials:
References: