Biomarkers in Patients With Metastatic Breast Cancer (BIOPEACE)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Identify the Number of Eligible Patients for Immunotherapy According to the Epidemiological and Biological Profile in Tunisia
• Intervention / Treatment: Diagnostic test: identify biomarkers

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

• Study Type: Observational
• Enrollment (Anticipated): 1600

Contacts and Locations

• Study Contact: Name: Monia Malek, MD; Phone Number: 00216 28 101 505; Email: monia.malek@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with metastatic or locally advanced breast cancer in Tunis, Tunisia.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of eligible patients for immunotherapy	Identify the number of eligible patients for immunotherapy according to the epidemiological and biological profile	2023 to 2027

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relevance of immunotherapy in Tunisia	Assess the relevance of the introduction of immunotherapy in Tunisia, by calculating the extension of the life expectancy (without disease and overall) of the patients who could benefit from this treatment, compared to the cost. - Identify the sub-population of patients who benefit most from immunotherapy in Tunisia	2023 to 2027

Collaborators and Investigators

• Sponsor: Tunisian Association for Immuno-oncology Research

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): June 1, 2027
• Study Completion (Anticipated): December 1, 2027

Study Registration Dates

• First Submitted: May 13, 2023
• First Submitted That Met QC Criteria: May 13, 2023
• First Posted (Actual): May 23, 2023

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 13, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: ECOCS2020-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No