Soft Tissue SarcomaNCT02547376
Genetic and Telomere Characteristics of High of Grade Soft Tissue Sarcomas
An observational study of Soft Tissue Sarcoma, run by University Hospitals, Leicester at 1 site in United Kingdom.
Trial summary
Soft tissue sarcomas (STSs) are a rare group of cancers that can arise in any 'soft' tissue but commonly involve muscles, fat and nerves. Even following surgery and radiotherapy over 50% of tumours will recur or spread and at present, there is no reliable test that allows doctors to predict in which patients this will… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Soft Tissue Sarcoma
- How many people
- 77 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 12 Feb 2015to 28 Sep 2020
- 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
- No healthy volunteers
- Adult, Older adult
Study population: Patient managed by East Midland Sarcoma Service with Soft Tissue Sarcoma undergoing attempted curative resection
Who may be able to join
- Cases of nonmetastatic biopsy proven highgrade soft tissue sarcoma (STS) presenting to the East Midlands Sarcoma Service
- Cases to be treated with curative intent with surgical resection (+/adjuvant therapy)
Who cannot join
- Cases presenting with local or distant recurrence
- Retroperitoneal soft tissue sarcomas
- Patients unable to provide informed consent
- Patients aged under 18
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospitals of Leicester NHS Trust
Leicester, Leicestershire, LE5 4PW
About this study
Soft tissue sarcomas (STSs) are a rare group of cancers that can arise in any 'soft' tissue but commonly involve muscles, fat and nerves. Even following surgery and radiotherapy over 50% of tumours will recur or spread and at present, there is no reliable test that allows doctors to predict in which patients this will occur.
DNA that is not inside cells (cell-free or cfDNA) is present in very small quantities circulating in blood. In cancer patients some of this cfDNA comes from cancer cells. Analysis of cancer-derived cfDNA in patients with other cancers has shown that the quantity and characteristics of cfDNA changes with stage of disease and treatment. The researchers plan to investigate the abundance and persistence of cancer-derived cfDNA in STS patients at various stages of disease to investigate the potential role of these characteristics as biomarkers.
Read more
Selection of the genetic characters to be tracked in the patients' cfDNA is an important consideration. An established hallmark of a cancer cell is the ability to undergo an unlimited number of cell divisions. In normal human cells protective structures on the ends of chromosomes called telomeres provide a mechanism to limit the number of times a healthy cell can divide. This limitation has to be overcome in cancer cells for a tumour to form. This occurs by the activation of one of two telomere maintenance mechanisms (TMM) - either an enzyme called Telomerase or a mechanism known as Alternative Lengthening of Telomeres (ALT). In many sarcomas the activation of either TMM is associated with genetic changes (mutations) in a small number of genes. As these mutations are not present in normal cells but mark an essential feature of cancer cells (and their capacity for unlimited cell division) they are likely to be reliable markers of the presence of STS cells.
The investigators plan to develop sensitive, quantitative assays to detect TMM associated mutations in tumour derived cfDNA in the blood of patients with STSs, and track these mutations overtime. They will establish the amount of cancer-derived cfDNA in STS patients at the time of surgery, and persistence of this cfDNA during follow up visits following tumour resection and in the events of local tumour recurrence or spread (metastatic disease). Once these basic parameters are established analysis will be broadened to include other genes that are commonly mutated in STSs with a view of identifying other genetic characteristics that may also aid identification of patients at high risk of recurrence or spread. In summary all of the assays described above should facilitate better monitoring of patients with STS, and allow earlier treatment if STS recurs following surgery.
Read the detailed description
Aims
The investigators plan a 2 year pilot observational study to:
- Identify and quantify circulating cell-fee DNA (cfDNA) in cases of Soft Tissue Sarcoma (STS)
- Investigate Telomere Maintenance Mechanisms (TMM) in STSs.
- Use TMM associated genetic mutations to identify and quantify tumour-derived cfDNA in STSs at time of tumour resection and throughout follow up
- Track the tumour derived cfDNA characteristics above over time and correlate with clinical outcome to identify potential STS biomarkers Hypotheses Based on findings in other cancers it is hypothesised that plasma cfDNA will be detectable in cases of STS. Given the key role telomere length maintenance plays in cancer cell development the investigators also hypothesise that TMM associated mutations will be present in tumour derived cfDNA, act as stable markers of STS tissue, and therefore increase in concentration as local recurrence or metastatic disease occurs.
Tumour derived cfDNA identification In months 0-3 sensitive assays to target known tumour-specific mutations will be developed. Using these on retrospectively collected tissues the investigators will verify that cfDNA can be detected (and quantified) in the plasma of patients with STSs.
Analysis of TMMs in STS tissue In months 3-12 tumour samples from every prospectively recruited sample will be analysed to establish which TMM is activated in STSs. Telomerase and ALT activity will each be assessed by published laboratory techniques.
Quantification and characterisation of TMM associated mutations / tumour derived cfDNA In months 10-12 quantitative Polymerase Chain Reaction based assays will be developed to identify the TMM associated mutations found to be most prevalent in STSs. In months 12-22 these assays will be used to identify and quantify these TMM associated mutations (and therefore also tumour-derived cfDNA) in the plasma samples taken from every prospectively recruited patient at time of surgery and throughout follow up.
Correlation of cfDNA characteristics with clinical outcome In months 22-24 cfDNA concentration, tumour-derived cfDNA concentration and the genetic characteristics of both will be correlated with clinical outcome measure including local recurrence, metastatic recurrence and death to determine these characteristics' potential as future biomarkers.
Patient recruitment / sample collection Patients will be recruited through the East Midlands Sarcoma Service. Samples already available will be collected from 2 sources to verify that cfDNA can be detected in STSs: Firstly 20 patients with metastatic disease will be asked to give consent for retrospective analysis of their tumour tissue already archived following histological analysis. One blood sample will also be collected from these patients for analysis. Secondly every STS sample already stored in the Nottingham Health Science Biobank, (Nottingham City Hospital) with an accompanying plasma sample also stored (15 at time of writing) will be analysed.
For the investigators remaining analysis between months 0-22 patients with non-metastatic high-grade STSs undergoing a planned resection locally will be approached to participate. 2013 figures suggest over 100 patients will be eligible for inclusion. Tumour tissue, blood, and unaffected muscle and saliva (2 sources of control DNA) will be collected at time of resection. Repeat blood samples will be collected 3 monthly until the end of recruitment.
- Conditions
- Soft Tissue Sarcoma
- Keywords
- Telomeres, Telomerase, Alternative lengthening of Telomeres Mechanism
- Medical subject headings
- Sarcoma
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 |
|---|---|---|
| Eligible patients with Soft Tissue Sarcoma | Primary Soft Tissue Sarcoma group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease recurrence (local and distant) post surgery
Measured: 18 months
Secondary outcomes (1)
Overall survival
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2015 (estimated)
- Study start12 Feb 2015
- Primary completion28 Sep 2020
- Study completion28 Sep 2020
Why it stopped: Covid-19
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Soft Tissue SarcomaStudies 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 only
- Time perspective
- Prospective
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals, Leicester
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02547376
- Sponsor's protocol ID
- UHL 11353
- Status last verified
- Oct 2020
- First submitted
- 18 Mar 2015
- Last updated
- 14 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic and Telomere Characteristics of High of Grade Soft Tissue Sarcomas
- ClinicalTrials.gov ID
- NCT02547376
- Acronym / sponsor ID
- UHL 11353
- Conditions
- Soft Tissue Sarcoma
- Keywords
- Telomeres, Telomerase, Alternative lengthening of Telomeres Mechanism
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Covid-19
- Enrolment
- 77 participants (actual)
- Lead sponsor
- University Hospitals, LeicesterUniversity, hospital or other
- Study start
- 12 Feb 2015 (actual)
- Primary completion
- 28 Sep 2020 (actual)
- Study completion
- 28 Sep 2020 (actual)
- First posted
- 11 Sep 2015 (estimated)
- 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.
Soft tissue sarcomas (STSs) are a rare group of cancers that can arise in any 'soft' tissue but commonly involve muscles, fat and nerves. Even following surgery and radiotherapy over 50% of tumours will recur or spread and at present, there is no reliable test that allows doctors to predict in which patients this will occur.
DNA that is not inside cells (cell-free or cfDNA) is present in very small quantities circulating in blood. In cancer patients some of this cfDNA comes from cancer cells. Analysis of cancer-derived cfDNA in patients with other cancers has shown that the quantity and characteristics of cfDNA changes with stage of disease and treatment. The researchers plan to investigate the abundance and persistence of cancer-derived cfDNA in STS patients at various stages of disease to investigate the potential role of these characteristics as biomarkers.
Selection of the genetic characters to be tracked in the patients' cfDNA is an important consideration. An established hallmark of a cancer cell is the ability to undergo an unlimited number of cell divisions. In normal human cells protective structures on the ends of chromosomes called telomeres provide a mechanism to limit the number of times a healthy cell can divide. This limitation has to be overcome in cancer cells for a tumour to form. This occurs by the activation of one of two telomere maintenance mechanisms (TMM) - either an enzyme called Telomerase or a mechanism known as Alternative Lengthening of Telomeres (ALT). In many sarcomas the activation of either TMM is associated with genetic changes (mutations) in a small number of genes. As these mutations are not present in normal cells but mark an essential feature of cancer cells (and their capacity for unlimited cell division) they are likely to be reliable markers of the presence of STS cells.
The investigators plan to develop sensitive, quantitative assays to detect TMM associated mutations in tumour derived cfDNA in the blood of patients with STSs, and track these mutations overtime. They will establish the amount of cancer-derived cfDNA in STS patients at the time of surgery, and persistence of this cfDNA during follow up visits following tumour resection and in the events of local tumour recurrence or spread (metastatic disease). Once these basic parameters are established analysis will be broadened to include other genes that are commonly mutated in STSs with a view of identifying other genetic characteristics that may also aid identification of patients at high risk of recurrence or spread. In summary all of the assays described above should facilitate better monitoring of patients with STS, and allow earlier treatment if STS recurs following surgery.
Detailed description
Aims
The investigators plan a 2 year pilot observational study to:
- Identify and quantify circulating cell-fee DNA (cfDNA) in cases of Soft Tissue Sarcoma (STS)
- Investigate Telomere Maintenance Mechanisms (TMM) in STSs.
- Use TMM associated genetic mutations to identify and quantify tumour-derived cfDNA in STSs at time of tumour resection and throughout follow up
- Track the tumour derived cfDNA characteristics above over time and correlate with clinical outcome to identify potential STS biomarkers Hypotheses Based on findings in other cancers it is hypothesised that plasma cfDNA will be detectable in cases of STS. Given the key role telomere length maintenance plays in cancer cell development the investigators also hypothesise that TMM associated mutations will be present in tumour derived cfDNA, act as stable markers of STS tissue, and therefore increase in concentration as local recurrence or metastatic disease occurs.
Tumour derived cfDNA identification In months 0-3 sensitive assays to target known tumour-specific mutations will be developed. Using these on retrospectively collected tissues the investigators will verify that cfDNA can be detected (and quantified) in the plasma of patients with STSs.
Analysis of TMMs in STS tissue In months 3-12 tumour samples from every prospectively recruited sample will be analysed to establish which TMM is activated in STSs. Telomerase and ALT activity will each be assessed by published laboratory techniques.
Quantification and characterisation of TMM associated mutations / tumour derived cfDNA In months 10-12 quantitative Polymerase Chain Reaction based assays will be developed to identify the TMM associated mutations found to be most prevalent in STSs. In months 12-22 these assays will be used to identify and quantify these TMM associated mutations (and therefore also tumour-derived cfDNA) in the plasma samples taken from every prospectively recruited patient at time of surgery and throughout follow up.
Correlation of cfDNA characteristics with clinical outcome In months 22-24 cfDNA concentration, tumour-derived cfDNA concentration and the genetic characteristics of both will be correlated with clinical outcome measure including local recurrence, metastatic recurrence and death to determine these characteristics' potential as future biomarkers.
Patient recruitment / sample collection Patients will be recruited through the East Midlands Sarcoma Service. Samples already available will be collected from 2 sources to verify that cfDNA can be detected in STSs: Firstly 20 patients with metastatic disease will be asked to give consent for retrospective analysis of their tumour tissue already archived following histological analysis. One blood sample will also be collected from these patients for analysis. Secondly every STS sample already stored in the Nottingham Health Science Biobank, (Nottingham City Hospital) with an accompanying plasma sample also stored (15 at time of writing) will be analysed.
For the investigators remaining analysis between months 0-22 patients with non-metastatic high-grade STSs undergoing a planned resection locally will be approached to participate. 2013 figures suggest over 100 patients will be eligible for inclusion. Tumour tissue, blood, and unaffected muscle and saliva (2 sources of control DNA) will be collected at time of resection. Repeat blood samples will be collected 3 monthly until the end of recruitment.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eligible patients with Soft Tissue Sarcoma | – | –Primary Soft Tissue Sarcoma group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patient managed by East Midland Sarcoma Service with Soft Tissue Sarcoma undergoing attempted curative resection
Key inclusion criteria (2 listed)
- Cases of nonmetastatic biopsy proven highgrade soft tissue sarcoma (STS) presenting to the East Midlands Sarcoma Service
- Cases to be treated with curative intent with surgical resection (+/adjuvant therapy)
Key exclusion criteria (4 listed)
- Cases presenting with local or distant recurrence
- Retroperitoneal soft tissue sarcomas
- Patients unable to provide informed consent
- Patients aged under 18
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
Disease recurrence (local and distant) post surgery
Time frame: 18 months
1 secondary outcome
Overall survival
Time frame: 18 months
Results and safety
The study was stopped early (reason given: Covid-19). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2020.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Soft Tissue Sarcoma, run by University Hospitals, Leicester at 1 site in United Kingdom.
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 2 inclusion and 4 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 14 Oct 2020. 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 United Kingdom. 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: Covid-19). 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?
Disease recurrence (local and distant) post surgery (time frame: 18 months). 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 14 Oct 2020.