Metastatic Breast Cancer
Conditions
Keywords
Luminal, HER2 negative, Endocrine therapy resistance
Brief summary
This is a multicentre, prospective, observational, no post-authorization study. This study will be opened for recruitment approximately for 12 months for a pilot phase including at least 25-30 patients and 6 controls and for 12 additional months to complete patient and control inclusion until 90 patients and 20 control depending on the first part study results.
Detailed description
After enrolment, patients will be assigned to one of the following cohorts according to their level of hormone-resistance: * Cohort A (hormone-sensitive disease). * Cohort B (hormone-resistant disease). In both cohorts it will be collected residual pre-treatment tumor samples from metastatic lesions, preferably obtained after last treatment just prior to study entry, and/or primary breast tumor; as well as serial blood samples at baseline, after 6 weeks, at the same time of radiological re-evaluation (3 months after ET initiation) and at progressive disease (PD) which will be used for serial analytic determinations of the expression profiles of Natural Killer (NK) cells, other lymphoid innate cells, NKG2D ligands, cytokines and other possible biomarkers; in addition to obtain local data of hemogram and estradiol, Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels. Patients who have participated in the study during their first line of ET are eligible to participate after progression, when they initiate the second line of ET (in this case, inclusion/exclusion criteria should be checked newly and Informed Consent Form (ICF) signed again). From the control population it will be collected blood and local data (e.g. hemogram, estradiol, FSH and LH levels), in a single time-point after ICF signature.
Interventions
None listed
Sponsors
Spanish Breast Cancer Research Group
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
INCLUSION AND
Exclusion criteria
OF PATIENTS Inclusion Criteria: 1. Female ≥ 18 years of age on day of signing informed consent. 2. Patient with histological confirmation of BC with evidence of metastatic or advanced disease not amenable to resection or radiation therapy with curative intent. 3. Documented Hormonal Receptor (HR) positive status based on local testing (preferably assessed on the most recent tumour biopsy available). HR+ is defined as ≥ 1% positive cells by immuno-histochemistry (IHC) for ER and/or Progesterone Receptor (PgR). 4. Documented HER2 negative status based on local testing (preferably assessed on the most recent tumour biopsy available). HER2- is defined as IHC score 0/1+ or negative by in situ hybridization according to local criteria. 5. Patients who are going to receive ET in first or second line for advanced disease (in monotherapy or in combination). It is allowed the inclusion of patients that have received or are going to initiate tamoxifen, Luteinizing Hormone Releasing Hormone (LHRH) analogues, aromatase inhibitors or fulvestrant. It is also possible to recruit patients that have received or are going to initiate cyclin or mTOR inhibitors in combination with ET. (NOTE: it is not allowed the inclusion of patients after first line of chemotherapy that are in response and initiate maintenance ET). 6. Patients who have participated in the study during their first line of ET are eligible to participate again when they receive the second line of ET (in this case eligibility criteria should be checked newly and ICF signed again). 7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. 8. Patient must have a life expectancy ≥ 16 weeks. 9. The patient has signed and dated the ICF for study participation. 10. Willingness and ability to comply with the protocol for the duration of the study including biological sample collection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amount of innate immune cells | Up to disease progression, an average of 25 months | Amount of the different populations of innate immune cells (e.g. NK cells, ILC1, ILC2 and ILC3) detected in tumor tissue and/or serial peripheral blood samples. Blood samples will be collected from the patients at the following time-points: at baseline, after 6 weeks, at tumor re-evaluation of treatment and after end of therapy (before the beginning of the next treatment). Blood samples will be collected from the control participants in a single time-point after signature of the corresponding Inform Consent Form. It is required the shipment of residual pre-treatment tumor samples (leftover from medical routine assistance) from primary and/or the recurrence/metastatic sites, preferably obtained after the last treatment prior to study entry. |
| Activation level of innate immune cells | Up to disease progression, an average of 25 months | Activation level of the different populations of innate immune cells (e.g. NK cells, ILC1, ILC2 and ILC3) detected in tumor tissue and/or serial peripheral blood samples. Blood samples will be collected from the patients at the following time-points: at baseline, after 6 weeks, at tumor re-evaluation of treatment and after end of therapy (before the beginning of the next treatment). Blood samples will be collected from the control participants in a single time-point after signature of the corresponding Inform Consent Form. It is required the shipment of residual pre-treatment tumor samples (leftover from medical routine assistance) from primary and/or the recurrence/metastatic sites, preferably obtained after the last treatment prior to study entry. |
| Analyses of the expression level of cytokines and/or rNKG2D ligands | Up to disease progression, an average of 25 months | Analyses of the expression level of cytokines and/or rNKG2D ligands in tumor tissue and/or serial peripheral blood samples. Blood samples will be collected from the patients at the following time-points: at baseline, after 6 weeks, at tumor re-evaluation of treatment and after end of therapy (before the beginning of the next treatment). Blood samples will be collected from the control participants in a single time-point after signature of the corresponding Inform Consent Form. It is required the shipment of residual pre-treatment tumor samples (leftover from medical routine assistance) from primary and/or the recurrence/metastatic sites, preferably obtained after the last treatment prior to study entry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) in relation with values of innate immune cells, cytokines and ligands of rNKG2D | Up to disease progression, an average of 25 months | Progression Free Survival (PFS) defined as the time from the start of therapy to the first documented progressive disease, or death from any cause, whichever occurs first. Progressive disease will be based on the investigator's assessment according to the standard institutional guidelines, and following as much as possible RECIST version 1.1. Tumor assessment during treatment will be performed according the clinical standard of care and following as much as possible RECIST version 1.1. every 3 months (+/- 1 month). |
| Objective Response Rate (ORR) in relation with values of innate immune cells, cytokines and ligands of rNKG2D | Up to disease progression, an average of 25 months | OR rate (ORR) is defined as the Complete Response (CR) + Partial Response (PR) out of the patients who had measurable disease at baseline, according to the standard institutional guidelines and following as much as possible the RECIST version 1.1. Tumor assessment during treatment will be performed according the clinical standard of care and following as much as possible RECIST version 1.1. every 3 months (+/- 1 month). |
| Clinical Benefit (CB) in relation with values of innate immune cells, cytokines and ligands of rNKG2D | Up to disease progression, an average of 25 months | Clinical Benefit (CB): is defined as complete response (CR), partial response (PR), or stable disease (SD) lasting more than 24 weeks; based on the investigator's assessment according to the standard institutional guidelines, and following as much as possible according to the RECIST version 1.1. The definition of Response/non-Response and Stable Disease will be based on the RECIST version 1.1. Tumor assessment during treatment will be performed according the clinical standard of care and following as much as possible RECIST version 1.1. every 3 months (+/- 1 month). |
Countries
Spain
Contacts
STUDY_DIRECTORStudy Director
Hospital General Universitario Morales Meseguer
Outcome results
None listed