Research and Analysis of the Mechanisms Involved in the Emergence of Breast Cancer Stem Cells (RepriM)

Breast Cancer Clinical Trial

Official title:

Research and Analysis of the Mechanisms Involved in the Emergence of Breast Cancer Stem Cells

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02570100
• Other study ID #: RepriM-1407
• Status: Terminated
• Phase: N/A
• Start date: April 2015
• Est. completion date: October 6, 2020

Study information

• Verified date: October 2021
• Source: Centre Oscar Lambret
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

From a cellular perspective, breast cancers appear to develop hierarchically from a small contingent of cancer stem cells (CSCs). The presence of CSCs in tumor tissue is associated with an increased risk of recurrence and metastasis, as well as a worse prognosis. Thus, these CSCs exhibit resistance to conventional anti-tumor treatments such as radiotherapy and chemotherapy. Moreover, these treatments would favor the emergence of these CSCs and the reprogramming of non-CSCs in CSCs. It has been demonstrated in neoadjuvant that the proportion of CSCs before any treatment is correlated with chemoresistance and that a resurgence of CSCs after chemotherapy is correlated with a poor prognosis. However, the mechanisms involved in the emergence of CSCs by reprogramming of non-CSCs are not yet known.

The Oscar Lambret Center proposes a monocentric prospective interventional study based on the cellular and molecular analysis of the tumor, serum and circulating cells, before, during and at the end of the treatment for each patient receiving a neoadjuvant chemotherapy for breast cancer. The identification of the mechanisms contributing to the enrichment of CSCs resistant to chemotherapy could lead to therapeutic solutions.

Description:

Patients responding criteria for selection will sign an informed consent form.

Before the initiation of chemotherapy, a tumor specimen (under echographic control) and four blood samples will be collected. The chemotherapy consists of 3 cycles of (F)EC100 spaced 21 days apart :

• Epirubicin, 100 mg/m² in intravenous (IV)

• Cyclophosphamide, 500 mg/m² in IV

• +/- 5-fluorouracile (5FU), 500 mg/m² in IV

Followed by 3 cycles of Taxotere (Docetaxel, IV, 100 mg/m²) spaced 21 days apart +/- Herceptin (Trastuzumab, IV, 8 mg/kg during C1 and then 6 mg/kg) for 1 year in the case of overexpression of the HER-2 oncoprotein.

After 3 cycles of chemotherapy (that is to say at the end of the (F)EC100 treatment, at the time of the usual ultrasound examination), a tumor specimen and four blood samples will be taken. After 6 cycles of chemotherapy (that is to say at the end of the Docetaxel +/- Trastuzumab treatment), four blood samples will be collected. A partial or total mastectomy could be performed during the 6 cycles of chemotherapy. During surgery, a tumor specimen will be taken. The indication of breast surgery will remain at the discretion of the pluridisciplinary committee of the participating center.

Prior to the start of treatment, patients will have a clinical and a paraclinical examination and will undergo laboratory examinations. On day 1 of the fourth cycle and after the sixth cycle of chemotherapy, patients will have a clinical examination and will undergo laboratory examinations. After three cycles of chemotherapy, at the time of the intermediate breast ultrasound, patients will have paraclinical examinations. Finally, at the end of the study (after partial or total mastectomy), anatomopathological examinations will be performed on the operative specimen.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 56
• Est. completion date: October 6, 2020
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Women over 18

• With a mammary adenocarcinoma histologically proven

• Who cannot benefit from a first-conserving surgery or with aggressiveness criteria on the initial biopsy (triple negative tumor, grade III histoprognostic, high Ki67, HER2 overexpressed) after presentation in multidisciplinary meeting.

• Absence of prior chemotherapy.

• Requiring a neoadjuvant chemotherapy with anthracyclines and taxanes selected in multidisciplinary meeting.

• Informed consent signed by the patient before the implementation of any specific procedure to the study.

Exclusion Criteria:

• Metastatic disease. The extension work-up is carried out according to the reference system of the participating center.

• Other histological type.

• Patient refusing the conservation of samples.

• Patient included in a clinical trial protocol with an experimental molecule (during this study).

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Procedure:
• Biological collection
Collection of blood samples and tumor specimens : Biological collection before treatment : 1 tumor specimen (under echographic control) 4 blood collections Biological collection during treatment : 1 tumor specimen after 3 cycles 4 blood collections after 3 and 6 cycles

Locations

Country	Name	City	State
France	Centre Oscar Lambret	Lille

Sponsors (3)

Lead Sponsor	Collaborator
Centre Oscar Lambret	Institut National de la Santé Et de la Recherche Médicale, France, Institut pour la Recherche sur le Cancer de Lille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete histopathological response	Complete histopathological response as classified by Sataloff according to the rate of CSCs before treatment.	1 month after surgery
Secondary	Evaluation of the expression of genes involved in reprogramming by immunohistochemistry and Reverse Transcription Polymerase Chain Reaction (RT-PCR) according to the rate of CSCs before, during and after chemotherapy.		Baseline
Secondary	Evaluation of the expression of genes involved in reprogramming by immunohistochemistry and Reverse Transcription Polymerase Chain Reaction (RT-PCR) according to the rate of CSCs before, during and after chemotherapy.		After 3 cycles (cycle length = 21 days) of chemotherapy
Secondary	Evaluation of the expression of genes involved in reprogramming by immunohistochemistry and Reverse Transcription Polymerase Chain Reaction (RT-PCR) according to the rate of CSCs before, during and after chemotherapy.		Within a month after surgery
Secondary	Evaluation of relapse-free survival	Evaluation of relapse-free survival, defined as the elapsed time between the date of diagnosis and the date of appearance of a local or distant recurrence.	1 month after surgery
Secondary	Quantification of the frequency of Cancer Stem Cells (CSCs) among the population of Circulating Tumor Cells (CTCs).		Baseline
Secondary	Quantification of the frequency of Cancer Stem Cells (CSCs) among the population of Circulating Tumor Cells (CTCs).		After 3 cycles (cycle length = 21 days) of chemotherapy
Secondary	Quantification of the frequency of Cancer Stem Cells (CSCs) among the population of Circulating Tumor Cells (CTCs).		After 6 cycles (cycle length = 21 days) of chemotherapy