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

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

This study assessed pasireotide LAR efficacy on patients with non-functioning pituitary adenomas concerning tumor growth.

Study Overview

• Status: Completed
• Conditions: Non-functioning Pituitary Adenoma
• Intervention / Treatment: Drug: Pasireotide LAR

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • CE
    • Fortaleza, CE, Brazil, 04636-000
      • Novartis Investigative Site
  • PR
    • Curitiba, PR, Brazil, 80030-110
      • Novartis Investigative Site
  • RJ
    • Rio de Janeiro, RJ, Brazil, 21941-913
      • Novartis Investigative Site
  • SC
    • Joinville, SC, Brazil, 89201260
      • Novartis Investigative Site
  • SP
    • Botucatu, SP, Brazil, 18618-970
      • Novartis Investigative Site
    • Sao Paulo, SP, Brazil, 05403 000
      • Novartis Investigative Site
    • Sao Paulo, SP, Brazil, 04023-900
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pasireotide LAR; All patients will receive pasireotide LAR (long acting release) 60 mg every 28 ± 3 days for 24 weeks	Drug: Pasireotide LAR; 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

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 26, 2012
• Primary Completion (ACTUAL): September 12, 2017
• Study Completion (ACTUAL): September 12, 2017

Study Registration Dates

• First Submitted: December 17, 2010
• First Submitted That Met QC Criteria: January 25, 2011
• First Posted (ESTIMATE): January 26, 2011

Study Record Updates

• Last Update Posted (ACTUAL): April 26, 2019
• Last Update Submitted That Met QC Criteria: April 24, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: tumor volume; pasireotide LAR,; Non-functioning pituitary adenoma,
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Adenoma; Pituitary Neoplasms; Pituitary Diseases; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pasireotide
• Other Study ID Numbers: CSOM230D2401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No