Biomarkers in Patients With Metastatic Breast Cancer

NCT ID: NCT05871788

Last Updated: 2023-05-23

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 1600 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-06-30
• Study Completion Date: 2027-12-31

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

Conditions

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

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Interventions

identify biomarkers

Identify the epidemiological profile of the biological signature (PD-L1 / TMB / MSI/HRD/ TILs) of patients with locally advanced or metastatic breast carcinoma

Intervention Type: DIAGNOSTIC_TEST

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Tunisian Association for Immuno-oncology Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Monia Malek, MD

Role: CONTACT

monia.malek@gmail.com

00216 28 101 505

Other Identifiers

ECOCS2020-01

Identifier Type: -

Identifier Source: org_study_id