Metastatic Breast CancerNIKOLENCT04370522
Characterization of Innate Immune System in Patients With Luminal Advanced Breast Cancer
An observational study of Metastatic Breast Cancer, run by Spanish Breast Cancer Research Group at 2 sites in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Metastatic Breast Cancer
- How many people
- 32 participants
- Where
- 2 sitesSpain
- Study dates
- 21 May 2021to 24 Mar 2025
- How long will I take part?
- 10 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Luminal/HER2 negative advanced Breast Cancer patients and a control group of healthy women (premenopausal and postmenopausal).
Who may be able to join
- Female ≥ 18 years of age on day of signing informed consent.
- Patient with histological confirmation of BC with evidence of metastatic or advanced disease not amenable to resection or radiation therapy with curative intent.
- 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).
- 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.
- 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).
- 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).
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- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
- Patient must have a life expectancy ≥ 16 weeks.
- The patient has signed and dated the ICF for study participation.
- Willingness and ability to comply with the protocol for the duration of the study including biological sample collection.
- Female ≥ 18 years of age on day of signing informed consent.
- The participant has signed and dated the ICF for study participation.
- Absence of evidences of current tumor malignancies or active infectious disease.
- Absence of history or current evidences of immunological and rheumatologic diseases or any condition, therapy, or laboratory abnormality that might confound the results of the study, in the opinion of the investigator.
- Willingness and ability to comply with blood and study data collection.
- To have data to be able to be classified as pre- o postmenopausal.
- Postmenopausal women are defined as women fulfilling any one of the following criteria (based on the National Comprehensive Cancer Network (NCCN) definition of menopause [NCCN 2008]):
- Prior bilateral oophorectomy.
- Age > 60 years.
- Age ≤ 60 years and with amenorrhea for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and FSH and estradiol in the postmenopausal range.
- Women who didn't comply with any of the prior criteria will be considered premenopausal women for the purposes of the study.
Who cannot join
- Have received more than 1 prior therapy line for advanced BC disease.
- Have received chemotherapy with response and initiate ET as maintenance treatment.
- Locally advanced breast cancer.
- Previous or concomitant treatment with immunotherapeutic agents.
- Major surgical procedure unrelated to breast cancer or significant traumatic injury within 28 days prior to study entry.
- History of concurrent or previously treated non-breast malignancies except for appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas, including cervix and colon.
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- Has a diagnosis of immunodeficiency, autoimmune disease or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of ET.
- Has an active infection requiring systemic therapy. Patients with solved infection that has finished antibiotic treatment within 7 days prior to study entry could be included.
- Has a known history of active Tuberculosis Bacillus (TB) or Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or a known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (HCV) (e.g. HCV RNA [qualitative] is detected).
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- There is evidence that the patient is pregnant or breastfeeding, or patient is expecting to conceive within the projected duration of the study.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the investigator.
- In the case of values of Neutrophil Count (NC) < 1.5 x 109/L prior to study entry or in case of patients who have received or are going to receive an investigational product, the information about NC or the investigational product should be checked with chief investigator in order to check any possible interference with the study results.
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
Hospital General Universitario Morales Meseguer
Murcia, 30008
Hospital Clínico Universitario de Valencia
Valencia, 46010
About this study
Official title: The NIKOLE Study: Characterization of Innate Immune System in Patients With Luminal Advanced Breast Cancer
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.
Read the 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.
- Conditions
- Metastatic Breast Cancer
- Keywords
- Luminal, HER2 negative, Endocrine therapy resistance
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: hormone-sensitive disease | Patients who initiate ET in first line of advanced disease, they could be patients de novo with no previous ET or patients who received adjuvant ET and experience disease recurrence more than one year after its completion. Patients will be divided in two subgroups according to having or not received previous ET. | |
| Cohort B: hormone-resistant disease | Patients in progression who are starting a first or second line of ET for advanced Breast Cancer (BC) and showing one of following the hormone-resistance criteria to any ET: For first line: * Primary hormone-resistance: disease recurrence occurs within the first two years of adjuvant ET. * Secondary hormone-resistance: disease recurrence occurs after the first two years of adjuvant ET or during the first year after its completion. For second line: * Primary hormone-resistance: disease progression occurs within the first 6 months of ET for advanced disease. * Secondary hormone-resistance: disease progression occurs after the first 6 months of ET for advanced disease. Patients will be divided in two subgroups according to having primary or secondary hormone-resistance. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amount of innate immune cells
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.
Measured: Up to disease progression, an average of 25 months
Activation level of innate immune cells
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.
Measured: Up to disease progression, an average of 25 months
Analyses of the expression level of cytokines and/or rNKG2D ligands
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.
Measured: Up to disease progression, an average of 25 months
Secondary outcomes (3)
Progression Free Survival (PFS) in relation with values of innate immune cells, cytokines and ligands of rNKG2D
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).
Measured: Up to disease progression, an average of 25 months
Objective Response Rate (ORR) in relation with values of innate immune cells, cytokines and ligands of rNKG2D
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).
Measured: Up to disease progression, an average of 25 months
Clinical Benefit (CB) in relation with values of innate immune cells, cytokines and ligands of rNKG2D
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).
Measured: Up to disease progression, an average of 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2020
- Study start21 May 2021
- Primary completion24 Mar 2025
- Study completion24 Mar 2025
Why it stopped: Lack of funding to continue the research into Phase II
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 32 participants (actual)
- Target duration
- 10 Years
Sponsor and investigators
- Lead sponsor
- Spanish Breast Cancer Research Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Hospital General Universitario Morales Meseguer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04370522
- Sponsor's protocol ID
- GEICAM/2018-03
- Acronym
- NIKOLE
- Status last verified
- Apr 2026
- First submitted
- 24 Apr 2020
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The NIKOLE Study: Characterization of Innate Immune System in Patients With Luminal Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT04370522
- Acronym / sponsor ID
- NIKOLE / GEICAM/2018-03
- Conditions
- Metastatic Breast Cancer
- Keywords
- Luminal, HER2 negative, Endocrine therapy resistance
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Lack of funding to continue the research into Phase II
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Spanish Breast Cancer Research GroupUniversity, hospital or other
- Study start
- 21 May 2021 (actual)
- Primary completion
- 24 Mar 2025 (actual)
- Study completion
- 24 Mar 2025 (actual)
- First posted
- 1 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 10 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A: hormone-sensitive disease | – | –Patients who initiate ET in first line of advanced disease, they could be patients de novo with no previous ET or patients who received adjuvant ET and experience disease recurrence more than one year after its completion. Patients will be divided in two subgroups according to having or not received previous ET. |
| Cohort B: hormone-resistant disease | – | –Patients in progression who are starting a first or second line of ET for advanced Breast Cancer (BC) and showing one of following the hormone-resistance criteria to any ET: For first line: * Primary hormone-resistance: disease recurrence occurs within the first two years of adjuvant ET. * Secondary hormone-resistance: disease recurrence occurs after the first two years of adjuvant ET or during the first year after its completion. For second line: * Primary hormone-resistance: disease progression occurs within the first 6 months of ET for advanced disease. * Secondary hormone-resistance: disease progression occurs after the first 6 months of ET for advanced disease. Patients will be divided in two subgroups according to having primary or secondary hormone-resistance. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Luminal/HER2 negative advanced Breast Cancer patients and a control group of healthy women (premenopausal and postmenopausal).
Key inclusion criteria (21 listed)
- Female ≥ 18 years of age on day of signing informed consent.
- Patient with histological confirmation of BC with evidence of metastatic or advanced disease not amenable to resection or radiation therapy with curative intent.
- 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).
- 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.
- 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).
Key exclusion criteria (13 listed)
- Have received more than 1 prior therapy line for advanced BC disease.
- Have received chemotherapy with response and initiate ET as maintenance treatment.
- Locally advanced breast cancer.
- Previous or concomitant treatment with immunotherapeutic agents.
- Major surgical procedure unrelated to breast cancer or significant traumatic injury within 28 days prior to study entry.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Amount of innate immune cells
Time frame: 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
Time frame: 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
Time frame: 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.
3 secondary outcomes
Progression Free Survival (PFS) in relation with values of innate immune cells, cytokines and ligands of rNKG2D
Time frame: Up to disease progression, an average of 25 months
Objective Response Rate (ORR) in relation with values of innate immune cells, cytokines and ligands of rNKG2D
Time frame: Up to disease progression, an average of 25 months
Clinical Benefit (CB) in relation with values of innate immune cells, cytokines and ligands of rNKG2D
Time frame: Up to disease progression, an average of 25 months
Results and safety
The study was stopped early (reason given: Lack of funding to continue the research into Phase II). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- GEICAM is the Spanish Breast Cancer Research GroupLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Hospital General Universitario Morales Meseguer
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Metastatic Breast Cancer, run by Spanish Breast Cancer Research Group at 2 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Lack of funding to continue the research into Phase II). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amount of innate immune cells (time frame: Up to disease progression, an average of 25 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026.