Thyroid CancerNCT03397238
Myeloid Cell Reprogramming in Thyroid Carcinoma
An observational study of Thyroid Cancer, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
This study investigates the reprogramming of myeloid cells in patients with thyroid carcinoma. The investigators hypothesize that tumor-derived factors change the function of myeloid cells (peripheral blood and bone marrow-derived) in such a way that these immune cells promote tumor growth rather than combat the tumor. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Thyroid Cancer
- How many people
- 41 participants
- Where
- 1 siteNetherlands
- Study dates
- 6 Mar 2018to 5 Jan 2021
- 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
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Primary care clinic
Who may be able to join
- Group 1:
- Subject is newly diagnosed with TC, therapy-naive and is planned to receive conventional treatment by surgery followed by RAI; no evidence of local or distant metastases
- Group 2:
- Subject has TC with evidence of distant metastases (either newly diagnosed or therapy-naive or patients with persistent or recurrent disease); at least 4 months since the previous treatment with RAI if applicable
- Group 3:
- Subject is diagnosed with MNG, is euthyroid, and is planned to undergo surgery - Group 4: Subject is diagnosed with MNG, is euthyroid, and is planned to receive RAI treatment
- Group 5: Healthy individuals who are euthyroid and have no evidence of thyroid disease
Who cannot join
- Mentally incompetent
- Pregnant, trying to become pregnant or breastfeeding
- Known inflammatory or infectious diseases or an immunosuppressive status
- Using medication interfering with the immune system
- Reduced platelet counts or other conditions associated with an increased risk of bleeding
- Severe comorbidities: other active malignancy (except for basal cell carcinoma)
- Serious psychiatric pathology
- A self-reported alcohol consumption of >21 units per week
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Myeloid Cell Reprogramming in the Context of Radioiodine Therapy in Patients With Non-Medullary Thyroid Carcinoma
This study investigates the reprogramming of myeloid cells in patients with thyroid carcinoma. The investigators hypothesize that tumor-derived factors change the function of myeloid cells (peripheral blood and bone marrow-derived) in such a way that these immune cells promote tumor growth rather than combat the tumor.
Read the detailed description
Description of the problem:
Non-medullary thyroid carcinoma (TC) is the most common endocrine malignancy and its incidence is one of the most rapidly increasing among the cancer types. For many patients with advanced and poorly differentiated tumors, treatment options are limited and the prognosis of advanced stage metastatic disease remains poor.
Envisioned solution/research direction:
To improve the patients outcome and identify novel therapeutic targets, one needs a 'systems understanding' of the pathophysiology of tumors, particularly the complex interaction of the malignant cells with other cell types in the tumor en the tumor environment (TME), especially immune cells. Tumor-associated macrophages (TAMs), the most dominant myeloid population in aggressive thyroid tumors, exhibit a distorted phenotype functioning predominantly as tumor enhancer. Despite the progress in understanding the importance of TAMs, the in-depth characterization of different TAMs populations is lacking and the mechanisms governing the functional polarization of TAMs are largely unknown. Understanding the interplay between TAMs and tumor cells represents a crucial step towards development of additional therapeutic strategies in cancer.
Hypothesis:
- We first propose that in advanced TC, not only TAMs, but also circulating monocytes and bone marrow (BM) myeloid progenitors are functionally reprogrammed by tumor-derived factors even before their recruitment in the TME.
- Radioactive iodide (I131)(RAI) is a very effective therapy for patients with TC, but is less effective in patients with advanced, metastatic tumors. We hypothesize that by exposing tumor antigens to the immune system, RAI might induce immunogenic effects at the level of the TME with reprogramming of both TAMs present in the TME and circulating monocytes, towards a tumor suppressive phenotype. This may further potentiate the effects of RAI. In addition this could be explored in the future as a basis for immunotherapy for tumors that are refractory to conventional treatment.
- Conditions
- Thyroid Cancer
- Keywords
- myeloid cell, reprogramming, monocyte, tumor-associated macrophage
- Medical subject headings
- Thyroid 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 |
|---|---|---|
| Non-metastatic TC | blood withdrawal, bone marrow aspiration | |
| Metastatic TC | blood withdrawal, bone marrow aspiration | |
| MNG surgery | blood withdrawal, bone marrow aspiration | |
| MNG RAI treatment | blood withdrawal | |
| Healthy volunteers | blood withdrawal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Transcriptional reprogramming of myeloid cells
RNAseq
Measured: baseline
Epigenetic reprogramming of myeloid cells
ATAC-seq
Measured: baseline
Functional reprogramming of myeloid cells
Cytokine response
Measured: baseline
Secondary outcomes (2)
Metabolites
Presence and level metabolites
Measured: baseline
Change of reprogramming after RAI treatment
RNAseq
Measured: baseline and 7 days after RAI treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2018
- Study start6 Mar 2018
- Primary completion26 Nov 2019
- Study completion5 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thyroid 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Romana T Netea-Maier, Principal investigator, Endocrinologist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03397238
- Sponsor's protocol ID
- NL62671.091.17
- Other IDs
- 2017-3628
- Status last verified
- Nov 2020
- First submitted
- 18 Dec 2017
- Last updated
- 9 Feb 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Myeloid Cell Reprogramming in the Context of Radioiodine Therapy in Patients With Non-Medullary Thyroid Carcinoma
- ClinicalTrials.gov ID
- NCT03397238
- Acronym / sponsor ID
- NL62671.091.17
- Conditions
- Thyroid Cancer
- Keywords
- myeloid cell, reprogramming, monocyte, tumor-associated macrophage
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 6 Mar 2018 (actual)
- Primary completion
- 26 Nov 2019 (actual)
- Study completion
- 5 Jan 2021 (actual)
- First posted
- 11 Jan 2018 (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 study investigates the reprogramming of myeloid cells in patients with thyroid carcinoma. The investigators hypothesize that tumor-derived factors change the function of myeloid cells (peripheral blood and bone marrow-derived) in such a way that these immune cells promote tumor growth rather than combat the tumor.
Detailed description
Description of the problem:
Non-medullary thyroid carcinoma (TC) is the most common endocrine malignancy and its incidence is one of the most rapidly increasing among the cancer types. For many patients with advanced and poorly differentiated tumors, treatment options are limited and the prognosis of advanced stage metastatic disease remains poor.
Envisioned solution/research direction:
To improve the patients outcome and identify novel therapeutic targets, one needs a 'systems understanding' of the pathophysiology of tumors, particularly the complex interaction of the malignant cells with other cell types in the tumor en the tumor environment (TME), especially immune cells. Tumor-associated macrophages (TAMs), the most dominant myeloid population in aggressive thyroid tumors, exhibit a distorted phenotype functioning predominantly as tumor enhancer. Despite the progress in understanding the importance of TAMs, the in-depth characterization of different TAMs populations is lacking and the mechanisms governing the functional polarization of TAMs are largely unknown. Understanding the interplay between TAMs and tumor cells represents a crucial step towards development of additional therapeutic strategies in cancer.
Hypothesis:
- We first propose that in advanced TC, not only TAMs, but also circulating monocytes and bone marrow (BM) myeloid progenitors are functionally reprogrammed by tumor-derived factors even before their recruitment in the TME.
- Radioactive iodide (I131)(RAI) is a very effective therapy for patients with TC, but is less effective in patients with advanced, metastatic tumors. We hypothesize that by exposing tumor antigens to the immune system, RAI might induce immunogenic effects at the level of the TME with reprogramming of both TAMs present in the TME and circulating monocytes, towards a tumor suppressive phenotype. This may further potentiate the effects of RAI. In addition this could be explored in the future as a basis for immunotherapy for tumors that are refractory to conventional treatment.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Non-metastatic TC | – | –blood withdrawal, bone marrow aspiration |
| Metastatic TC | – | –blood withdrawal, bone marrow aspiration |
| MNG surgery | – | –blood withdrawal, bone marrow aspiration |
| MNG RAI treatment | – | –blood withdrawal |
| Healthy volunteers | – | –blood withdrawal |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Primary care clinic
Key inclusion criteria (7 listed)
- Group 1:
- Subject is newly diagnosed with TC, therapy-naive and is planned to receive conventional treatment by surgery followed by RAI; no evidence of local or distant metastases
- Group 2:
- Subject has TC with evidence of distant metastases (either newly diagnosed or therapy-naive or patients with persistent or recurrent disease); at least 4 months since the previous treatment with RAI if applicable
- Group 3:
Key exclusion criteria (8 listed)
- Mentally incompetent
- Pregnant, trying to become pregnant or breastfeeding
- Known inflammatory or infectious diseases or an immunosuppressive status
- Using medication interfering with the immune system
- Reduced platelet counts or other conditions associated with an increased risk of bleeding
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
Transcriptional reprogramming of myeloid cells
Time frame: baseline
RNAseq
Epigenetic reprogramming of myeloid cells
Time frame: baseline
ATAC-seq
Functional reprogramming of myeloid cells
Time frame: baseline
Cytokine response
2 secondary outcomes
Metabolites
Time frame: baseline
Change of reprogramming after RAI treatment
Time frame: baseline and 7 days after RAI treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2022.
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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.
Romana T Netea-Maier principal investigator
Endocrinologist
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Thyroid Cancer, run by Radboud University Medical Center at 1 site in Netherlands.
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 7 inclusion and 8 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: finished, as of the sponsor's last update on 9 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Transcriptional reprogramming of myeloid cells (time frame: baseline). 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 9 Feb 2022.