Evaluate the Efficacy and Safety of Pasireotide LAR (Long Acting Release) on the Treatment of Patients With Clinically Non-Functioning Pituitary Adenoma.

Study Overview
=================
Brief Summary
-----------------
This study assessed pasireotide LAR efficacy on patients with non-functioning pituitary adenomas concerning tumor growth.

Official Title
-----------------
An Open-Label, Single Arm, Phase II Study to Evaluate the Efficacy and Safety of Pasireotide LAR on the Treatment of Patients With Clinically Non-Functioning Pituitary Adenoma

Conditions
-----------------
Non-functioning Pituitary Adenoma

Intervention / Treatment
-----------------
* Drug: Pasireotide LAR


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Non-functioning pituitary adenoma ≥ 1cm, patients without any previous treatment for the tumor Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Exclusion Criteria: Patients who required a surgical intervention for relief of any sign or symptom associated with tumor compression Previous pituitary surgery Previous medical treatment for pituitary tumor Patients who had received pituitary irradiation within 10 years prior to randomization Prolactin (PRL) levels > 100 ng/mL. PRL evaluation should have been performed with diluted samples to ensure hook effect. was avoided Patients who presented prolactinomas, acromegaly or Cushing's disease Patients with compression of the optic chiasm causing acute clinically significant visual field defects

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pasireotide LAR<br>All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks | Drug: Pasireotide LAR<br>* 20 and 40 mg of powder in vials and 2 mL of vehicle in ampoules (for reconstitution) administered as a depot intragluteal IM (intramuscular) injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Non-functioning Pituitary Adenomas (NFPA) Who Achieve Tumor Volume Reduction of at Least 20% After 24 Weeks (FAS) | Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility.The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. A change ≥ 20% in the original volume of the tumor was considered to be clinically significant. Evaluable participants required tumor volume assessment at baseline and at week 24. | Baseline up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Volume Main Phase (FAS) | Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. | baseline to week 4, 12, 24 | 
| Tumor Volume in Extension Phase (FAS) | Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. | baseline to week 48, 72, 96 | 
| Tumor Volume Change From Baseline in Main Phase (FAS) | Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. | baseline to week 4, 12, 24 | 
| Tumor Volume Change From Baseline in Extension Phase (FAS) | Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. | baseline to week 48, 72, 96 | 
| Tumor Volume Percent Change From Baseline in Main Phase (FAS) | Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. | baseline to week 4, 12, 24 | 
| Tumor Volume Percent Change From Baseline in Extension Phase (FAS) | Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. | baseline to week 48, 72, 96 | 
| Percentage of Patients Achieving Tumour Volume Reduction in Main Phase (FAS) | Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. | baseline to week 4, 12, 24 | 
| Percentage of Patients Achieving Tumour Volume Reduction of at Least ≥ 20% in Main Phase (FAS) | Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. | baseline to week 4, 12, 24 | 
| Percentage of Patients Achieving Tumour Volume Reduction in Extension Phase (FAS) | Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. | baseline to week 48, 72, 96 | 
| Percentage of Patients Achieving Tumour Volume Reduction of at Least ≥ 20% in Extension Phase (FAS) | Tumor volume was evaluated by MRI. MRIs were performed and processed according to the guidelines of the central evaluator's facility. The pituitary adenomas were measured by a neuro-radiologist, using manual tracing together with the imaging analysis software. The largest diameter at any plan determined the maximum diameter of the tumor. | baseline to week 48, 72, 96 | 
| Percentage of Participants Reporting Absence and Presence of Relevant Disease-related Symptoms (FAS) | The absence and presence of disease-related symptoms were reported by patients and recorded by the medical staff. Patients classified the symptoms according to a 5-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe | Baseline and at weeks 4, 12,24,48,72, 96 | 
| Mean GH and IGF-1 Hormone Levels During Main and Extension Phases (FAS) | Hormone levels, including those of GH, IGF-1, and prolactin were evaluated by a central lab | Baseline and at weeks 24, 48, 96 | 
| Mean ACTH and Estradiol Hormone Levels During Main and Extension Phases (FAS) | Hormone levels, including those of growth hormone (GH),insulin-like growth factor 1 (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, cortisol, free thyroxine (free T4), and estradiol (for women) or testosterone (for men), were evaluated by a central lab | Baseline and at weeks 24, 48, 96 | 
| Mean Cortisol Hormone Levels During Main and Extension Phases (FAS) | Hormone levels, including those of GH, IGF-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, cortisol, free T4, and estradiol (for women) or testosterone (for men), were evaluated by a central lab | Baseline and at weeks 24, 48, 96 | 
| Mean LH and FSH Hormone Levels During Main and Extension Phases (FAS) | Hormone levels, including those of GH, IGF-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, cortisol, free T4, and estradiol (for women) or testosterone (for men), were evaluated by a central lab | Baseline and at weeks 24, 48, 96 | 
| Mean Testosterone and Free T4 Hormone Levels During Main and Extension Phases (FAS) | Hormone levels, including those of GH, IGF-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, cortisol, free T4, and estradiol (for women) or testosterone (for men), were evaluated by a central lab | Baseline and at weeks 24, 48, 96 | 
| Mean TSH Hormone Levels During Main and Extension Phases (FAS) | Hormone levels, including those of GH, IGF-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, cortisol, free T4, and estradiol (for women) or testosterone (for men), were evaluated by a central lab | Baseline and at weeks 24, 48, 96 | 
| Mean Alpha Subunit Levels in Main and Extension Phases (FAS) |  | Baseline and at weeks 12,24,48,72, 96 | 
| Percentage of Participants With Reduction From Baseline of Alpha Subunit ≥50% in Main and Extension Phases (FAS) | Alpha subunit levels were determined at a central laboratory. | Baseline up to approximately Week 96 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Non-functioning pituitary adenoma,, pasireotide LAR,, tumor volume