Pituitary TumorsPITUIGENENCT01903967
Identification of GENEtic Markers of Aggressiveness and Malignancy by Array Comparative Genomic Hybrization Analysis (CGH)
An observational study of Pituitary Tumors, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Recent studies estimate that the prevalence of pituitary adenomas is approximately 1/1500 persons. Pituitary tumours are usually considered as benign. However, local invasion is reported in 35-40% of pituitary adenomas; resistance to medical treatment or recurrence leading to multimodal therapy is reported in about… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Pituitary Tumors
- How many people
- 213 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2013to Jan 2017
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients presenting a pituitary tumour, including PRL, GH, ACTH and LH/FSH, operated on by transsphenoidal route between 1990 and 2008 with at least 5 years of follow-up
Who may be able to join
- Only patient with complete clinical, radiological and hormonal data available during yearly follow-up will be included.
- Preoperative MRI will be used to classify the tumour as invasive, and postoperative MRI will be collected to confirm recurrence or progression of the tumour.
- Presence of tumour fragments fixed in Holland-Bouin's fluid or Neutral Buffered Formalin fixative available for aCGH analysis.
Who cannot join
- Patient who underwent systematic post-operative radiotherapy.
- Patient presenting Multiple Endocrine Neoplasia type 1 (MEN1) or aryl hydrocarbon receptor interacting protein (AIP) mutation since mechanism of tumorigenesis are different to sporadic pituitary tumours.
Trial locations and contacts
1 site in 1 country.
About this study
Recent studies estimate that the prevalence of pituitary adenomas is approximately 1/1500 persons. Pituitary tumours are usually considered as benign. However, local invasion is reported in 35-40% of pituitary adenomas; resistance to medical treatment or recurrence leading to multimodal therapy is reported in about 15% of cases. These tumours are considered as aggressive pituitary tumours and present a distinct biological and clinical entity with continued growth despite multimodal therapy, including surgery and radiotherapy (McCormack et al., 2011). Whilst these tumours have malignant potential, the term of pituitary carcinoma is strictly reserved for those rare tumours (0.2%) with demonstrated craniospinal or systemic metastases (Heaney, 2011).
Pituitary aggressive and malignant tumours are very difficult to control and ultimately prove to be lethal. It was suggested that early aggressive treatments (chemotherapy, radiotherapy) may control progression and occurrence of metastases. However, these therapeutic options are associated with important side effects limiting their use and the prediction of pituitary tumor behaviour remains a challenge. At the diagnosis, clinical signs are not specific and the results concerning proliferative factors (Ki-67 and P53), putative oncogenes (PTTG) conflict from one series to another.
Read more
In a case-control retrospective study of a cohort of 410 patients (HYPOPRONOS), we validated a prognostic pathological classification based on histological and radiological data (J. Trouillas 2012 in preparation). Tumours were classified into 3 grades: grade 1= non-invasive tumour, grade 2= invasive tumour and grade 3 = aggressive-invasive tumor with the combination of radiological signs of invasion and 2 of 3 signs of increased proliferation (Ki-67 index>3%, number of mitoses>2 per 10 fields at 400X, P53 nuclear detection).
It is now widely accepted that cancer is a clonal disease, which arises from a single normal cell and progresses thanks to the accumulation of DNA alterations (Sanson et al., 2011). To identify the role of these DNA alterations, we conducted array CGH analysis limited to 13 prolactin pituitary tumours, from frozen fragments, and identified allelic loss of chromosome 11 associated with aggressiveness and malignancy (Wierinckx et al., 2011).
To confirm these encouraging results we propose to conduct a study on a large series of tumours, fixed and embed, and to be correlated the results to clinical data.
- Conditions
- Pituitary Tumors
- Keywords
- Pituitary, CGH array, Tumor
- Medical subject headings
- Pituitary Neoplasms, Pituitary Diseases, 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 |
|---|---|---|
| "Control" Group | Patients cured with no evidence of disease up to 5 years will be the controls. | |
| "Case" Group | Patients, in recurrence or progression before 5 years will be the cases |
What is being measured
The primary outcome is the main question the study is designed to answer.
DNA alterations associated with the prognosis of pituitary tumours.
To identify and quantify the genomic DNA alterations associated with the prognosis of pituitary tumours.
Measured: At least 5 years of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2013 (estimated)
- Study startSep 2013
- Primary completionJan 2017
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pituitary TumorsStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 213 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gérald RAVEROT, PhD - MD, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01903967
- Sponsor's protocol ID
- D50834
- Acronym
- PITUIGENE
- Status last verified
- Jan 2017
- First submitted
- 17 Jul 2013
- Last updated
- 23 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Lasolle H, Raverot G. Letter to the Editor From Helene Lasolle and Gerald Raverot: "USP8 and TP53 Drivers Are Associated With CNV in a Corticotroph Adenoma Cohort Enriched for Aggressive Tumors". J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3285-e3286. doi: 10.1210/clinem/dgab217. No abstract available.
PubMed 33822961Lasolle H, Alix E, Bonnefille C, Elsensohn MH, Michel J, Sanlaville D, Roy P, Raverot G, Bardel C. Centralization errors in comparative genomic hybridization array analysis of pituitary tumor samples. Genes Chromosomes Cancer. 2018 Jun;57(6):320-328. doi: 10.1002/gcc.22534. Epub 2018 Mar 9.
PubMed 29460398
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of GENEtic Markers of Aggressiveness and Malignancy by Array Comparative Genomic Hybrization Analysis (CGH)
- ClinicalTrials.gov ID
- NCT01903967
- Acronym / sponsor ID
- PITUIGENE / D50834
- Conditions
- Pituitary Tumors
- Keywords
- Pituitary, CGH array, Tumor
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 213 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Sep 2013
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 19 Jul 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.
Recent studies estimate that the prevalence of pituitary adenomas is approximately 1/1500 persons. Pituitary tumours are usually considered as benign. However, local invasion is reported in 35-40% of pituitary adenomas; resistance to medical treatment or recurrence leading to multimodal therapy is reported in about 15% of cases. These tumours are considered as aggressive pituitary tumours and present a distinct biological and clinical entity with continued growth despite multimodal therapy, including surgery and radiotherapy (McCormack et al., 2011). Whilst these tumours have malignant potential, the term of pituitary carcinoma is strictly reserved for those rare tumours (0.2%) with demonstrated craniospinal or systemic metastases (Heaney, 2011).
Pituitary aggressive and malignant tumours are very difficult to control and ultimately prove to be lethal. It was suggested that early aggressive treatments (chemotherapy, radiotherapy) may control progression and occurrence of metastases. However, these therapeutic options are associated with important side effects limiting their use and the prediction of pituitary tumor behaviour remains a challenge. At the diagnosis, clinical signs are not specific and the results concerning proliferative factors (Ki-67 and P53), putative oncogenes (PTTG) conflict from one series to another.
In a case-control retrospective study of a cohort of 410 patients (HYPOPRONOS), we validated a prognostic pathological classification based on histological and radiological data (J. Trouillas 2012 in preparation). Tumours were classified into 3 grades: grade 1= non-invasive tumour, grade 2= invasive tumour and grade 3 = aggressive-invasive tumor with the combination of radiological signs of invasion and 2 of 3 signs of increased proliferation (Ki-67 index>3%, number of mitoses>2 per 10 fields at 400X, P53 nuclear detection).
It is now widely accepted that cancer is a clonal disease, which arises from a single normal cell and progresses thanks to the accumulation of DNA alterations (Sanson et al., 2011). To identify the role of these DNA alterations, we conducted array CGH analysis limited to 13 prolactin pituitary tumours, from frozen fragments, and identified allelic loss of chromosome 11 associated with aggressiveness and malignancy (Wierinckx et al., 2011).
To confirm these encouraging results we propose to conduct a study on a large series of tumours, fixed and embed, and to be correlated the results to clinical data.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| "Control" Group | – | –Patients cured with no evidence of disease up to 5 years will be the controls. |
| "Case" Group | – | –Patients, in recurrence or progression before 5 years will be the cases |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients presenting a pituitary tumour, including PRL, GH, ACTH and LH/FSH, operated on by transsphenoidal route between 1990 and 2008 with at least 5 years of follow-up
Key inclusion criteria (3 listed)
- Only patient with complete clinical, radiological and hormonal data available during yearly follow-up will be included.
- Preoperative MRI will be used to classify the tumour as invasive, and postoperative MRI will be collected to confirm recurrence or progression of the tumour.
- Presence of tumour fragments fixed in Holland-Bouin's fluid or Neutral Buffered Formalin fixative available for aCGH analysis.
Key exclusion criteria (2 listed)
- Patient who underwent systematic post-operative radiotherapy.
- Patient presenting Multiple Endocrine Neoplasia type 1 (MEN1) or aryl hydrocarbon receptor interacting protein (AIP) mutation since mechanism of tumorigenesis are different to sporadic pituitary tumours.
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
DNA alterations associated with the prognosis of pituitary tumours.
Time frame: At least 5 years of follow-up
To identify and quantify the genomic DNA alterations associated with the prognosis of pituitary tumours.
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 23 Jan 2017.
- Derived from this study: PubMed 33822961Lasolle H, Raverot G. Letter to the Editor From Helene Lasolle and Gerald Raverot: "USP8 and TP53 Drivers Are Associated With CNV in a Corticotroph Adenoma Cohort Enriched for Aggressive Tumors". J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3285-e3286. doi: 10.1210/clinem/dgab217. No abstract available.
- Derived from this study: PubMed 29460398Lasolle H, Alix E, Bonnefille C, Elsensohn MH, Michel J, Sanlaville D, Roy P, Raverot G, Bardel C. Centralization errors in comparative genomic hybridization array analysis of pituitary tumor samples. Genes Chromosomes Cancer. 2018 Jun;57(6):320-328. doi: 10.1002/gcc.22534. Epub 2018 Mar 9.
- Related InfoLink 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.
Gérald RAVEROT, PhD - MD principal investigator
Hospices Civils de Lyon
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 Pituitary Tumors, run by Hospices Civils de Lyon at 1 site in France.
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 3 inclusion and 2 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 23 Jan 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 France. 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?
DNA alterations associated with the prognosis of pituitary tumours. (time frame: At least 5 years of follow-up). 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 NCT01903967, which also lists 2 linked publications.
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 23 Jan 2017.