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Acromegaly Resistant to Conventional Dose of First Generation Somatostatin Ligands

Completed
Conditions
Acromegaly
Interventions
Registration Number
NCT06607666
Lead Sponsor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Brief Summary

Acromegaly is a chronic disease, with a high frequency of systemic complications and reduced life span, in cases of persistently active disease. The remission of acromegaly through the surgical removal of the pituitary adenoma ranges from the 10 to 70%, according to surgery experience, tumor invasion and dimension. The medical treatment can reach the control of acromegaly disease in around 35-45% of patients treated with first generation somatostatin analogues (first gen-SSAs) at standard dose. Instead, patients partially or completely resistant to treatment with first gen-SSAs may reach the control of acromegaly by treatments with high dose/frequency first gen-SSAs, antagonist of GH receptor and second generation SSAs. At the actual moment, the scientific societies are heavily working for reaching definitive guidelines for the management of second line treatments in acromegaly patients resistant to first gen-SSAs at standard dose. According to the most recent expert opinions, consensus and guidelines, the choice of second line treatment may be oriented by patients' comorbidities and molecular characterization of the GH secreting tumors. However, a consensus of the clinical use of molecular biomarkers was not reached.

The primary objective of this study is to define the number of patients who had reached the control of acromegaly at 6, 12 and 24 months of treatment, according to the following two treatment schemes (Lanreotide ATG at conventional dose versus Lanreotide ATG at high dose/frequency). The secondary objectives are to evaluate the role of the tumor molecular biomarkers, clinical and biochemical features of acromegaly and of morphological features of GH secreting tumors in predicting the outcome of the previous detailed two treatment schemes.

For reaching these aims, we designed an observational, retrospective, mono-center study on acromegaly patients. Patients will be enrolled according to strict inclusion/exclusion criteria. Data collection will be retrospectively conducted on molecular biomarkers (e.g. genomic polymorphism of the gene of the GH receptor on patients' blood; expression of GH, prolactin, Ki-67 labeling index (Li), p53, subtype 2 and 5 of the somatostatin receptor, cytokeratin pattern and number of mitosis through immunohistochemistry on paraffin-fixed samples of the patients' pituitary GH secreting tumors) and on clinical (e.g. gender and age at acromegaly diagnosis) and biochemical features (e.g. random GH, cycle GH and GH nadir, IGF-I, prolactin values at the time of acromegaly diagnosis, after pituitary surgery and before starting treatment with first gen-SSAs). The results of these clinical, biochemical and morphological markers will be correlated to the outcome of treatment with Lanreotide ATG, both at standard dose and at high dose/high frequency.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
102
Inclusion Criteria
  • patients diagnosed for acromegaly;
  • patients underwent first line treatment for acromegaly with pituitary surgery;
  • patients with acromegaly diagnosis confirmed through the pathological examination of the resected pituitary tumor;
  • patients affected by persistently active acromegaly, after pituitary surgery and consecutively treated with Lanreotide ATG at standard dose;
  • patients treated with Lanreotide ATG at standard dose for at least 12 consecutive months and/or patients treated with Lanreotide ATG at standard dose for 6 consecutive months and then at high dose/frequency for at least 12 consecutive month;
  • cases with available of all data, required for this study in internal database.
Exclusion Criteria
  • patients underwent medical therapies or radiotherapy before pituitary surgery;
  • patients underwent radiotherapy within 3 years before starting the treatment with Lanreotide ATG;
  • patients on treatment with other drugs for acromegaly as dopamine agonist and/or antagonist of GH receptor.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Low dose to fg-SRLsLanreotide autogelPatients responsive to low dose to fg-SRLs
High dose to fg-SRLsLanreotide autogelPatients responsive to high dose to fg-SRLs
Other treatmentsLanreotide autogelPatients not responsive to low/high dose of fg-SRLs
Primary Outcome Measures
NameTimeMethod
Lanreotide ATG efficacy24 months

number of patients who had reached the control of acromegaly at 6, 12 and 24 months of treatment

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Fondazione Policlinico Universitario Agostino Gemelli IRCCS, UOC ENDOCRINOLOGIA

🇮🇹

Roma, Italy

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