Endometrial CancerNCT03466034
The Role of Hypoxia as a Selective Pressure for TP53 Mutations
An observational study of Endometrial Cancer, run by Institute of Cancer Research, United Kingdom at 1 site in United Kingdom.
Trial summary
The study aims to develop scans that tell the investigators about the oxygen content of tumours using Magnetic Resonance Imaging (MRI) and seeing whether regions of low oxygen content are related to mutations in cancer genes such as TP53. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Endometrial Cancer
- How many people
- 5 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 6 Feb 2018to 30 Jul 2019
- 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
- No healthy volunteers
- Adult, Older adult
Study population: Participants scheduled to have hysterectomy at the cancer centre
Who may be able to join
- ≥18 years of age on the day of signing the informed consent.
- Histologically confirmed endometroid or serous endometrial cancer.
- Scheduled to have hysterectomy at the cancer centre
- Identifiable tumour mass on staging MRI.
- Voluntarily agreed to participate by giving written informed consent.
Who cannot join
- Life expectancy of < 6 months.
- Ferromagnetic implants, contraindicating MRI
- Claustrophobia so unable to tolerate MRI
- Unable to lie flat
- Ascites sufficient to prevent patient being fitted in the scanner bore
- Histology unlikely to show variation in TP53 status, or heavily calcified disease.
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- Radiotherapy to the abdomen or pelvis within 6 months of the screening visit.
- Unresolved bowel obstruction.
- Currently participating or has participated in a study with an investigational compound or device within 30 days of the start of treatment.
- History or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with patient's participation for the full duration of the study, or is not in the best interest of the patient to participate.
- Unlikely to comply with the requirements of the study.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
The Institute of Cancer Research & The Royal Marsden NHS Foundation Trust
Sutton, Surrey, SM2 5PT
About this study
The study aims to develop scans that tell the investigators about the oxygen content of tumours using Magnetic Resonance Imaging (MRI) and seeing whether regions of low oxygen content are related to mutations in cancer genes such as TP53. MRI is a method of obtaining pictures of inside of the body that shows the appearance and structure of soft tissues.
To get the information about the oxygen content of tumours, MRI is carried out while breathing 100% oxygen. The variation of oxygen supply to different regions of the tumour will help the investigators to predict tumour behavior and tumour response to treatment.
Read the detailed description
Cancer tissue harbours a multitude of genetic alterations, and it is well-established that when certain key alterations develop, they are powerful determinants of tumour behaviour (growth rate, potential to spread). One of the most sinister and well-recognized alterations is in a gene called TP53. Another feature of tumours that results in resistance to treatment and poor outcome is a low oxygen level within tumour tissue. However, whether alterations in TP53 are driven by low oxygen levels is not established.
Endometrial cancer is a good model to study the relationship between low tumour oxygen levels and alterations in TP53 within tumour. Firstly, it is a common gynaecological malignancy, (9,300 new cases annually in the UK) with two recognized types based on the appearance and behaviour of the tumour. In type I (endometrioid and mucinous carcinomas), alterations in TP53 are uncommon (15%), while in type II (serous and clear cell carcinomas) they are common (88%). In-line with this, the survival of patients with Type 2 cancer is worse. Secondly, endometrial cancer is routinely assessed at diagnosis using Magnetic Resonance Imaging. This non-invasive scanning technique can be manipulated to derive additional information about the oxygen status of the whole tumour and regions within it. Finally, the primary management of endometrial cancer is surgical and involves hysterectomy. This means it is possible to obtain fresh tumour tissue at the time of surgery from regions that have been identified on imaging as having low vs.high levels of oxygen and to establish their TP53 status. In this study, therefore, the investigator will establish the regional oxygen distribution within endometrial cancers at diagnosis, and relate them to the alterations in TP53 from fresh tissue samples from selected regions using gene sequencing. Understanding how highly deleterious mutations arise in cancer might provide new avenues for intervention and control.
- Conditions
- Endometrial Cancer
- Keywords
- TP53, Hypoxia, Endometriod and Mucinous Carcinomas, Serous and Clear Cell Carcinomas, Magnetic Resonance Imaging, MRI
- Medical subject headings
- Endometrial Neoplasms, Hypoxia, Adenocarcinoma, Mucinous
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 |
|---|---|---|
| Endometriod | Type I (endometrioid and mucinous carcinomas) - Magnetic Resonance Imaging (MRI) with 100% Oxygen. | |
| Serous | Type II (serous and clear cell carcinomas) - Magnetic Resonance Imaging (MRI) with 100% Oxygen. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Establish distinctive patterns of distribution and expression of mutant TP53 between tumour regions with differing levels of oxygenation (as measured by R2*on MRI).
Determined at post surgery histology
Measured: Duration of study (24 months)
Secondary outcomes (2)
The reproducibility of the R2* measurement, assessed by comparing 2 R2* scans per person
comparison of image data at conclusion of MRI scan
Measured: 6 months
Establish the range of intratumoral heterogeneity of the R2* measurement within individual tumours
comparison of image data at conclusion of MRI scan
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2018
- Study start6 Feb 2018
- Primary completion19 Jun 2018
- Study completion30 Jul 2019
Why it stopped: Low numbers of eligible patients and failure to successfully recruit them.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometrial CancerStudies of the same condition, open and under way.
- More trials run by Institute of Cancer Research, United KingdomThe sponsor's other registered studies.
- 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
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Cancer Research, United Kingdom
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research UK
- Responsible party
- Principal investigator, Nandita deSouza, Institute of Cancer Research, United Kingdom
- Investigators
- Nandita deSouza, Principal investigator, The Institution of Cancer Research & The Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03466034
- Sponsor's protocol ID
- CCR 4784
- Status last verified
- Jan 2020
- First submitted
- 12 Feb 2018
- Last updated
- 29 Jan 2020
- 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 29 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Hypoxia as a Selective Pressure for TP53 Mutations
- ClinicalTrials.gov ID
- NCT03466034
- Acronym / sponsor ID
- CCR 4784
- Conditions
- Endometrial Cancer
- Keywords
- TP53, Hypoxia, Endometriod and Mucinous Carcinomas, Serous and Clear Cell Carcinomas, Magnetic Resonance Imaging, MRI
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Low numbers of eligible patients and failure to successfully recruit them.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Institute of Cancer Research, United KingdomUniversity, hospital or other
- Collaborators
- Cancer Research UK
- Study start
- 6 Feb 2018 (actual)
- Primary completion
- 19 Jun 2018 (actual)
- Study completion
- 30 Jul 2019 (actual)
- First posted
- 15 Mar 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.
The study aims to develop scans that tell the investigators about the oxygen content of tumours using Magnetic Resonance Imaging (MRI) and seeing whether regions of low oxygen content are related to mutations in cancer genes such as TP53. MRI is a method of obtaining pictures of inside of the body that shows the appearance and structure of soft tissues.
To get the information about the oxygen content of tumours, MRI is carried out while breathing 100% oxygen. The variation of oxygen supply to different regions of the tumour will help the investigators to predict tumour behavior and tumour response to treatment.
Detailed description
Cancer tissue harbours a multitude of genetic alterations, and it is well-established that when certain key alterations develop, they are powerful determinants of tumour behaviour (growth rate, potential to spread). One of the most sinister and well-recognized alterations is in a gene called TP53. Another feature of tumours that results in resistance to treatment and poor outcome is a low oxygen level within tumour tissue. However, whether alterations in TP53 are driven by low oxygen levels is not established.
Endometrial cancer is a good model to study the relationship between low tumour oxygen levels and alterations in TP53 within tumour. Firstly, it is a common gynaecological malignancy, (9,300 new cases annually in the UK) with two recognized types based on the appearance and behaviour of the tumour. In type I (endometrioid and mucinous carcinomas), alterations in TP53 are uncommon (15%), while in type II (serous and clear cell carcinomas) they are common (88%). In-line with this, the survival of patients with Type 2 cancer is worse. Secondly, endometrial cancer is routinely assessed at diagnosis using Magnetic Resonance Imaging. This non-invasive scanning technique can be manipulated to derive additional information about the oxygen status of the whole tumour and regions within it. Finally, the primary management of endometrial cancer is surgical and involves hysterectomy. This means it is possible to obtain fresh tumour tissue at the time of surgery from regions that have been identified on imaging as having low vs.high levels of oxygen and to establish their TP53 status. In this study, therefore, the investigator will establish the regional oxygen distribution within endometrial cancers at diagnosis, and relate them to the alterations in TP53 from fresh tissue samples from selected regions using gene sequencing. Understanding how highly deleterious mutations arise in cancer might provide new avenues for intervention and control.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Endometriod | – | –Type I (endometrioid and mucinous carcinomas) - Magnetic Resonance Imaging (MRI) with 100% Oxygen. |
| Serous | – | –Type II (serous and clear cell carcinomas) - Magnetic Resonance Imaging (MRI) with 100% Oxygen. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Participants scheduled to have hysterectomy at the cancer centre
Key inclusion criteria (5 listed)
- ≥18 years of age on the day of signing the informed consent.
- Histologically confirmed endometroid or serous endometrial cancer.
- Scheduled to have hysterectomy at the cancer centre
- Identifiable tumour mass on staging MRI.
- Voluntarily agreed to participate by giving written informed consent.
Key exclusion criteria (11 listed)
- Life expectancy of < 6 months.
- Ferromagnetic implants, contraindicating MRI
- Claustrophobia so unable to tolerate MRI
- Unable to lie flat
- Ascites sufficient to prevent patient being fitted in the scanner bore
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
Establish distinctive patterns of distribution and expression of mutant TP53 between tumour regions with differing levels of oxygenation (as measured by R2*on MRI).
Time frame: Duration of study (24 months)
Determined at post surgery histology
2 secondary outcomes
The reproducibility of the R2* measurement, assessed by comparing 2 R2* scans per person
Time frame: 6 months
Establish the range of intratumoral heterogeneity of the R2* measurement within individual tumours
Time frame: 6 months
Results and safety
The study was stopped early (reason given: Low numbers of eligible patients and failure to successfully recruit them.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 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.
Nandita deSouza principal investigator
The Institution of Cancer Research & The Royal Marsden NHS Foundation Trust
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 Endometrial Cancer, run by Institute of Cancer Research, United Kingdom 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 5 inclusion and 11 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 29 Jan 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: Low numbers of eligible patients and failure to successfully recruit them.). 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?
Establish distinctive patterns of distribution and expression of mutant TP53 between tumour regions with differing levels of oxygenation (as measured by R2*on MRI). (time frame: Duration of study (24 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 29 Jan 2020.