PROSTATE CANCERPhase 1/2PROGENYNCT02022371
Prostate Cancer Genomic Heterogeneity
A Phase 1/2 study testing Targeted biopsies of the prostate in people with PROSTATE CANCER, run by University College London Hospitals at 1 site in United Kingdom.
Trial summary
The purpose of this study is to carry out very detailed genetic testing on prostate cancer cells. The reason to do this is because researchers do not fully understand How prostate cancer develops Why some cancer cells spread and others do not Why some cancer cells respond to treatment and others do not Researchers and… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- PROSTATE CANCER
- What is being tested?
- Targeted biopsies of the prostate
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2014to Jun 2016
- Phase
- Phase 1/2
- 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
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Treatment naïve group
- Men with no prior diagnosis of prostate cancer undergoing prostate biopsy based on identified lesions on imaging
- Men with a raised PSA above 15ng/ml
- Men giving informed consent
- Treated men
- Men undergoing tissue biopsy for suspicion of prostate cancer recurrence following previous local or systemic therapy based on identified lesions in multi-parametric MRI, bone-scan, choline PET/CT, or PET/MRI
Who cannot join
- 1. Unable to have MRI scan or CT scan, or in whom artefact would reduce scan quality
- Unable to have prostate biopsy
- Unable to undergo biopsy for metastatic evaluation
- On immunosuppression or predefined immunosuppressed state
- A coagulopathy predisposing to bleeding
- Unable to give informed consent
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University College London Hospitals
London, NW1 2BU
About this study
The purpose of this study is to carry out very detailed genetic testing on prostate cancer cells. The reason to do this is because researchers do not fully understand
- How prostate cancer develops
- Why some cancer cells spread and others do not
- Why some cancer cells respond to treatment and others do not
Read more
Researchers and doctors know that 1 in 3 of the male population over the age of 50 has cancer cells in their prostate. However, most of these men will never know they have it and it will not affect their quality of life or their life expectancy. However, some cancers can be aggressive. These are more likely to spread outside of the prostate and cause problems. Doctors do not have an accurate way to tell the difference between aggressive cancer and those which will not cause any problems. Even within one prostate some tumours are aggressive and others do not cause a problem during the lifetime of a patient. In fact, even within one tumour, different cells may behave differently. In other words, one part of the tumour may be aggressive and spread, whilst another part of the same tumour does not. This project will try to find out more about what makes different tumours and different parts of the same tumour aggressive or harmless.
It is important to find out what makes some cancer cells spread and others stay where they are. For the investigators to do this they need to collect fresh samples of cancer tissue from the prostate and from different areas of a tumour within the prostate. This is because biopsies used to diagnose or exclude cancer by the hospital laboratory are not good enough to give investigators detailed genetic information. These biopsies have been put into a chemical called formalin which reduces the quality of the genetic information.
Investigators are therefore asking patients who are undergoing prostate biopsies as part of their normal care to allow them to take additional biopsies for the purpose of this study. This may be the first time patients are having biopsies. Or, patients may be having biopsies after treatment that has been given for the cancer and the doctors are concerned the treatment is not working.
Read the detailed description
Cancer is a genetic disease, caused by mutations in genes that lead to increased cell proliferation and survival. Importantly, the genetic changes vary dramatically between individual prostate cancer patients and the specific combination of mutations within a patient's cancer is thought to determine tumour aggressiveness and clinical outcome.
Personalized medicine approaches aim to decipher the genetic code of a patient's tumour in order to identify cancers which will behave aggressively and need treatment. However, extensive intra-tumour heterogeneity (ITH) has been discovered in several solid tumour types, complicating the identification of the relevant genetic changes as they may not be present throughout the entire tumour and are likely to be missed by tumour biopsies. ITH is thus a major hurdle for the implementation of personalized cancer treatment approaches.
Investigators have developed genetic technologies that allow them to measure ITH in solid tumours and they now want to apply these to patients with prostate cancer to define the extent and the clinical importance of ITH in this disease which is currently unknown. This will involve looking at the control of genes in the cancer cells which make some tumours more aggressive than others. This may help in predicting which tumours are important and need to be targeted and those that could be left so that too much tissue damage does not occur as a result of therapy. Finding out why some cancer cells spread and others do not may also help to identify novel molecular targets that could be used to prevent the development of metastases.
Patients with suspected prostate cancer usually have scans and then prostate biopsies. These biopsies are needed by the pathologist to make a proper diagnosis and cannot be used for full genetic analysis. So, investigators will ask patients whether they would be willing to give some extra samples of tissue while undergoing these routine biopsies.
Defining ITH in prostate cancer will provide important insights into the genetics of prostate cancer development and metastatic progression and is a key prerequisite for the development of reliable personalized cancer medicine approaches. Thus this study will significantly advance researchers' efforts to predict which tumours are dangerous and in need of urgent treatment and those that could safely be left untreated which would spare these patients the unnecessary side effects. Investigators think that this research work will have a major impact on the use of next generation sequencing in the management of prostate cancer through an in-depth understanding of how common are differences between and within individual cancer lesions. Investigators also want to find out whether these differences, if they exist, are important in tumour development and spread to other areas. Investigators think that the characterization of these differences will allow them to successfully use this information to group patients undergoing treatment using molecular 'signatures' so that treatment is targeted rather than applied in a 'sledge-hammer' approach. Investigators believe that without studies like PROGENY, doctors will instead rely on data from single tumour biopsies which can be misleading since single biopsies may not have sampled the most aggressive tumour area. Finally, investigators think that PROGENY will reveal how prostate cancers evolve over time and which of these changes lead to metastases and ultimately kill the patient. These are called phylogenetic studies and will help work out the main (or 'trunk') genomic changes from later events in 'branches'. This may allow researchers to focus their drug discovery efforts on the common 'trunk' genomic changes.
- Conditions
- PROSTATE CANCER
- Being tested
- Targeted biopsies of the prostate
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeted biopsies of the prostateProcedure or surgery
Also called SmartTarget Biopsies of the prostate for snap frozen tissue in order to obtain genetic heterogeneity
Multiple biopsies from a MRI lesion for analysis of intratumour heterogeneity
| Study group | Role | What they receive |
|---|---|---|
| Targeted biopsy | Experimental | Snap frozen targeted biopsies of the prostate for genomic analysis Receives: Procedure: Targeted biopsies of the prostate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumour heterogeneity
To define the extent of inter/intra-tumour heterogeneity and its association with disease stage at diagnosis and Gleason grade by deep genomic sequencing of multiple regions of intermediate Gleason grade tumours and high Gleason grade tumours, with and without metastatic disease.
Measured: At time of biopsy
Clonal origin of secondary tumours
Through clonal re-ordering and multi-regional prostate mapping, determine whether satellite tumour nodules in high grade prostate cancers represent monoclonal disease related to the index lesion or the evolution of polyclonal cancers by evaluating the deep genomic signatures of primary and secondary lesions within the prostate
Measured: At time of biopsy
Relationship of tumours to metastases
Identify genotype requirements for metastasis development by deep sequencing DNA from the associated metastases from the same patient to reconstruct clonal evolution from primary tumour to metastatic sites and identify evolutionary bottlenecks governing metastasis development that may be targetable for clinical benefit.
Measured: At time of biopsy
Secondary outcomes (3)
Identifying genomic signature of tumour DNA in blood
To determine whether ultra-deep sequencing of circulating plasma DNA can reconstruct inter/intra-tumour heterogeneity and clonal evolution occurring in men who have failed first- and second-line therapies (for localized and metastatic disease).
Measured: At time of biopsy
Genomic signature changes in tumour DNA in blood when drug resistance develops
To determine whether ultra-deep sequencing of circulating plasma DNA can reconstruct inter/intra-tumour heterogeneity and clonal evolution occurring during the acquisition of castration resistant disease.
Measured: At time of biopsy
Relationship of tumour genomics with imaging
To determine the association of inter/intra-tumour heterogeneity with functional imaging with multi-parametric magnetic resonance imaging
Measured: At time of biopsy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2013 (estimated)
- Study startSep 2014
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PROSTATE 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College London Hospitals
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hashim Uddin Ahmed, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02022371
- Sponsor's protocol ID
- 13/0244
- Acronym
- PROGENY
- Status last verified
- May 2017
- First submitted
- 15 Dec 2013
- Last updated
- 10 May 2017
- Results posted
- No
Publications
Linch M, Goh G, Hiley C, Shanmugabavan Y, McGranahan N, Rowan A, Wong YNS, King H, Furness A, Freeman A, Linares J, Akarca A, Herrero J, Rosenthal R, Harder N, Schmidt G, Wilson GA, Birkbak NJ, Mitter R, Dentro S, Cathcart P, Arya M, Johnston E, Scott R, Hung M, Emberton M, Attard G, Szallasi Z, Punwani S, Quezada SA, Marafioti T, Gerlinger M, Ahmed HU, Swanton C. Intratumoural evolutionary landscape of high-risk prostate cancer: the PROGENY study of genomic and immune parameters. Ann Oncol. 2017 Oct 1;28(10):2472-2480. doi: 10.1093/annonc/mdx355.
PubMed 28961847
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prostate Cancer Genomic Heterogeneity
- ClinicalTrials.gov ID
- NCT02022371
- Acronym / sponsor ID
- PROGENY / 13/0244
- Conditions
- PROSTATE CANCER
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University College London HospitalsUniversity, hospital or other
- Study start
- Sep 2014 (actual)
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 27 Dec 2013 (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.
The purpose of this study is to carry out very detailed genetic testing on prostate cancer cells. The reason to do this is because researchers do not fully understand
- How prostate cancer develops
- Why some cancer cells spread and others do not
- Why some cancer cells respond to treatment and others do not
Researchers and doctors know that 1 in 3 of the male population over the age of 50 has cancer cells in their prostate. However, most of these men will never know they have it and it will not affect their quality of life or their life expectancy. However, some cancers can be aggressive. These are more likely to spread outside of the prostate and cause problems. Doctors do not have an accurate way to tell the difference between aggressive cancer and those which will not cause any problems. Even within one prostate some tumours are aggressive and others do not cause a problem during the lifetime of a patient. In fact, even within one tumour, different cells may behave differently. In other words, one part of the tumour may be aggressive and spread, whilst another part of the same tumour does not. This project will try to find out more about what makes different tumours and different parts of the same tumour aggressive or harmless.
It is important to find out what makes some cancer cells spread and others stay where they are. For the investigators to do this they need to collect fresh samples of cancer tissue from the prostate and from different areas of a tumour within the prostate. This is because biopsies used to diagnose or exclude cancer by the hospital laboratory are not good enough to give investigators detailed genetic information. These biopsies have been put into a chemical called formalin which reduces the quality of the genetic information.
Investigators are therefore asking patients who are undergoing prostate biopsies as part of their normal care to allow them to take additional biopsies for the purpose of this study. This may be the first time patients are having biopsies. Or, patients may be having biopsies after treatment that has been given for the cancer and the doctors are concerned the treatment is not working.
Detailed description
Cancer is a genetic disease, caused by mutations in genes that lead to increased cell proliferation and survival. Importantly, the genetic changes vary dramatically between individual prostate cancer patients and the specific combination of mutations within a patient's cancer is thought to determine tumour aggressiveness and clinical outcome.
Personalized medicine approaches aim to decipher the genetic code of a patient's tumour in order to identify cancers which will behave aggressively and need treatment. However, extensive intra-tumour heterogeneity (ITH) has been discovered in several solid tumour types, complicating the identification of the relevant genetic changes as they may not be present throughout the entire tumour and are likely to be missed by tumour biopsies. ITH is thus a major hurdle for the implementation of personalized cancer treatment approaches.
Investigators have developed genetic technologies that allow them to measure ITH in solid tumours and they now want to apply these to patients with prostate cancer to define the extent and the clinical importance of ITH in this disease which is currently unknown. This will involve looking at the control of genes in the cancer cells which make some tumours more aggressive than others. This may help in predicting which tumours are important and need to be targeted and those that could be left so that too much tissue damage does not occur as a result of therapy. Finding out why some cancer cells spread and others do not may also help to identify novel molecular targets that could be used to prevent the development of metastases.
Patients with suspected prostate cancer usually have scans and then prostate biopsies. These biopsies are needed by the pathologist to make a proper diagnosis and cannot be used for full genetic analysis. So, investigators will ask patients whether they would be willing to give some extra samples of tissue while undergoing these routine biopsies.
Defining ITH in prostate cancer will provide important insights into the genetics of prostate cancer development and metastatic progression and is a key prerequisite for the development of reliable personalized cancer medicine approaches. Thus this study will significantly advance researchers' efforts to predict which tumours are dangerous and in need of urgent treatment and those that could safely be left untreated which would spare these patients the unnecessary side effects. Investigators think that this research work will have a major impact on the use of next generation sequencing in the management of prostate cancer through an in-depth understanding of how common are differences between and within individual cancer lesions. Investigators also want to find out whether these differences, if they exist, are important in tumour development and spread to other areas. Investigators think that the characterization of these differences will allow them to successfully use this information to group patients undergoing treatment using molecular 'signatures' so that treatment is targeted rather than applied in a 'sledge-hammer' approach. Investigators believe that without studies like PROGENY, doctors will instead rely on data from single tumour biopsies which can be misleading since single biopsies may not have sampled the most aggressive tumour area. Finally, investigators think that PROGENY will reveal how prostate cancers evolve over time and which of these changes lead to metastases and ultimately kill the patient. These are called phylogenetic studies and will help work out the main (or 'trunk') genomic changes from later events in 'branches'. This may allow researchers to focus their drug discovery efforts on the common 'trunk' genomic changes.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Targeted biopsy | Experimental | Procedure: Targeted biopsies of the prostateSnap frozen targeted biopsies of the prostate for genomic analysis |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Treatment naïve group
- Treated men
- Men undergoing tissue biopsy for suspicion of prostate cancer recurrence following previous local or systemic therapy based on identified lesions in multi-parametric MRI, bone-scan, choline PET/CT, or PET/MRI
Key exclusion criteria (6 listed)
- Unable to have prostate biopsy
- Unable to undergo biopsy for metastatic evaluation
- On immunosuppression or predefined immunosuppressed state
- A coagulopathy predisposing to bleeding
- Unable to give informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Targeted biopsies of the prostateAlso: SmartTarget Biopsies of the prostate for snap frozen tissue in order to obtain genetic heterogeneityMultiple biopsies from a MRI lesion for analysis of intratumour heterogeneity | Procedure or surgery | Targeted biopsy |
Primary outcome
Tumour heterogeneity
Time frame: At time of biopsy
To define the extent of inter/intra-tumour heterogeneity and its association with disease stage at diagnosis and Gleason grade by deep genomic sequencing of multiple regions of intermediate Gleason grade tumours and high Gleason grade tumours, with and without metastatic disease.
Clonal origin of secondary tumours
Time frame: At time of biopsy
Through clonal re-ordering and multi-regional prostate mapping, determine whether satellite tumour nodules in high grade prostate cancers represent monoclonal disease related to the index lesion or the evolution of polyclonal cancers by evaluating the deep genomic signatures of primary and secondary lesions within the prostate
Relationship of tumours to metastases
Time frame: At time of biopsy
Identify genotype requirements for metastasis development by deep sequencing DNA from the associated metastases from the same patient to reconstruct clonal evolution from primary tumour to metastatic sites and identify evolutionary bottlenecks governing metastasis development that may be targetable for clinical benefit.
3 secondary outcomes
Identifying genomic signature of tumour DNA in blood
Time frame: At time of biopsy
Genomic signature changes in tumour DNA in blood when drug resistance develops
Time frame: At time of biopsy
Relationship of tumour genomics with imaging
Time frame: At time of biopsy
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 10 May 2017.
- Derived from this study: PubMed 28961847Linch M, Goh G, Hiley C, Shanmugabavan Y, McGranahan N, Rowan A, Wong YNS, King H, Furness A, Freeman A, Linares J, Akarca A, Herrero J, Rosenthal R, Harder N, Schmidt G, Wilson GA, Birkbak NJ, Mitter R, Dentro S, Cathcart P, Arya M, Johnston E, Scott R, Hung M, Emberton M, Attard G, Szallasi Z, Punwani S, Quezada SA, Marafioti T, Gerlinger M, Ahmed HU, Swanton C. Intratumoural evolutionary landscape of high-risk prostate cancer: the PROGENY study of genomic and immune parameters. Ann Oncol. 2017 Oct 1;28(10):2472-2480. doi: 10.1093/annonc/mdx355.
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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?
A Phase 1/2 study testing Targeted biopsies of the prostate in people with PROSTATE CANCER, run by University College London Hospitals 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 6 inclusion and 6 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 10 May 2017. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Tumour heterogeneity (time frame: At time of biopsy). 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?
On the ClinicalTrials.gov record for NCT02022371, which also lists 1 linked publication.
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 10 May 2017.