Identification of GENEtic Markers of Aggressiveness and Malignancy by Array Comparative Genomic Hybrization Analysis (CGH)

Pituitary Tumors Clinical Trial

— PITUIGENE  

Official title:

Identification of GENEtic Markers of Aggressiveness and Malignancy by Array Comparative Genomic Hybrization Analysis (CGH)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01903967
• Other study ID #: D50834
• Status: Completed
• Phase: N/A
• First received: July 17, 2013
• Last updated: January 20, 2017
• Start date: September 2013
• Est. completion date: January 2017

Study information

• Verified date: January 2017
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 213
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Aggression
• Pituitary Diseases
• Pituitary Neoplasms
• Pituitary Tumors

Locations

Country	Name	City	State
France	Hospices Civils de Lyon - Groupement Hospitalier Est	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DNA alterations associated with the prognosis of pituitary tumours.	To identify and quantify the genomic DNA alterations associated with the prognosis of pituitary tumours.	At least 5 years of follow-up

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