Study of Pasireotide in Patients With Rare Tumors of Neuroendocrine Origin

An Open Label, Multicenter, Single Arm Study of Pasireotide LAR in Patients With Rare Tumors of Neuroendocrine Origin

This study will assess the effectiveness and safety of pasireotide long-acting release in patients who have rare tumors of neuroendocrine origin.

Study Overview

• Status: Terminated
• Conditions: Pituitary Neoplasm; Pancreatic Neoplasm; Ectopic ACTH Syndrome; Nelson Syndrome
• Intervention / Treatment: Drug: pasireotide LAR

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1264AAA
    • Novartis Investigative Site
• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Novartis Investigative Site
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Novartis Investigative Site
• Brazil
  • CE
    • Fortaleza, CE, Brazil, 60430-370
      • Novartis Investigative Site
  • MG
    • Belo Horizonte, MG, Brazil, 30130-100
      • Novartis Investigative Site
  • SP
    • Botucatu, SP, Brazil, 18618-970
      • Novartis Investigative Site
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H2L 2W5
      • Novartis Investigative Site
• France
  • Angers, France, 49033
    • Novartis Investigative Site
  • Bron Cedex, France, 69677
    • Novartis Investigative Site
  • Le Kremlin Bicetre, France, 94275
    • Novartis Investigative Site
  • Lille Cedex, France, 59037
    • Novartis Investigative Site
  • Marseille cedex 05, France, 13385
    • Novartis Investigative Site
  • Pessac Cedex, France, 33604
    • Novartis Investigative Site
  • Reims, France, 51092
    • Novartis Investigative Site
  • Strasbourg, France, 67098
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10098
    • Novartis Investigative Site
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Muenchen, Germany, 80804
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Würzburg, Germany, 97080
    • Novartis Investigative Site
• Italy
  • AN
    • Ancona, AN, Italy, 60126
      • Novartis Investigative Site
  • FE
    • Cona, FE, Italy, 44100
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35128
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56124
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00168
      • Novartis Investigative Site
• Mexico
  • Distrito Federal
    • México, Distrito Federal, Mexico, 14269
      • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Novartis Investigative Site
  • Moscow, Russian Federation, 117036
    • Novartis Investigative Site
  • Saint-Petersburg, Russian Federation, 197341
    • Novartis Investigative Site
• Spain
  • Andalucia
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center Cedars Sinai 4
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center The Pituitary Center (3)
    • Stanford, California, United States, 94304
      • Stanford University Medical Center SC
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute Deptof DanaFarberCancerInst(5)
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine Study Coordinator
  • Washington
    • Seattle, Washington, United States
      • Swedish Medical Center Dept.ofSwedishMedicalCtr.(2)

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:

• Male and Female Patients at least 18 years old

• Patient who have rare tumors of neuroendocrine origin, such as tumors of the:

  1. pancreas
  2. pituitary glands
  3. Nelson syndrome
  4. ectopic-ACTH secreting tumor
• Patients who have failed standard of care treatment or for whom no standard of care treatment exist
• Signed Informed Consent

Exclusion Criteria:

• Patients with active gallbladder disease
• Patients with any ongoing or planned anti-neoplastic or interferon therapy
• Poorly controlled diabetes mellitus
• Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pasireotide LAR 60mg; Patients received pasireotide LAR at 60 mg approximately once every 28 days for 6 months during the core treatment period and additional treatment cycles up to a total of 48 months during the extension phase.	Drug: pasireotide LAR; Investigational drug pasireotide LAR was supplied in vials with 20 mg or 40 mg powder and 2 mL vehicle was supplied in ampoules for reconstitution.; Other Names: SOM230

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Responders at Month 6 - Pooled Pancreatic NETs (PNETs)	The primary efficacy endpoint was defined as the percentage of responders at Month 6 among pooled PNET patients (insulinoma, gastrinoma, VIPoma, and glucagonoma). A responder was defined as a patient who either attained normalization or had a greater than 50% reduction from baseline of the level of the primary biochemical tumor marker at Month 6 (M6). Four insulinoma pts were excluded from analysis because of unavailability of normal ranges for the associated primary biochemical tumor marker (insulin-to-glucose ratio). One patient with VIPoma with a normal baseline was also excluded. As a result, only 20 out of 25 patients with PNET were included in the assessment of the primary endpoint, which was less than the planned sample size of 34. Therefore, the primary objective could not be assessed with sufficient power. Patients with missing Month 6 assessment were considered as non-responders. Responder analyses are reported only for indications with minimum of 6 patients.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Responders at Month 6 - Individual NETs	Percentage of responders for each of the 10 NET indications considered in the study. Responder analyses were performed for an indication only if there were at least 6 patients in the efficacy analyzable set. For all other individual indications, the numbers of patients in the efficacy analyzable sets were less than 6 and therefore no responder analyses were carried out for these indications.	6 months
Percentage of Responders With Probability of Success at Month 6 - Individual NETs	Percentage of responders for each of the 10 NET indications considered in the study. Responder analyses were performed for an indication only if there were at least 6 patients in the efficacy analyzable set. For all other individual indications, the numbers of patients in the efficacy analyzable sets were less than 6 and therefore no responder analyses were carried out for these indications. The probability of success was a chance that the true responder rate was greater than 15%) for the indications gastrinoma, prolactinoma, and Nelson's syndrome.	6 months
PNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker	Specific primary biochemical tumor markers were used to assess the efficacy of pasireotide in PNETs. A Month 6 responder was defined as the patients who either attained normalization or greater than 50% reduction from baseline in the level of the primary biochemical tumor marker at Month 6. One gastrinoma patient had a missing primary tumor marker value at Month 6, but had a Month 5 assessment done on Day 141, which fell within the allowed window period for Month 6.	Baseline, month 6
PiNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker	Specific primary biochemical tumor markers were used to assess the efficacy of pasireotide in PNETs. A Month 6 responder was defined as the patients who either attained normalization or greater than 50% reduction from baseline in the level of the primary biochemical tumor marker at Month 6.	Baseline, month 6
Nelson's Syndrome: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker	Six patients with Nelson's syndrome met the responder's criteria of attaining normalization or a reduction of more than 50% in primary tumor marker at Month 6.	Baseline, month 6

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: July 22, 2009
• First Submitted That Met QC Criteria: August 11, 2009
• First Posted (Estimate): August 13, 2009

Study Record Updates

• Last Update Posted (Estimate): July 26, 2016
• Last Update Submitted That Met QC Criteria: June 15, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Pancreatic neoplasm; pasireotide LAR; pituitary neoplasm; Rare tumors of neuroendocrine origin; NETs of the pancreatic; Pituitary NETs; EAS Tumors; Nelson's Syndrome; Nelson Syndrome; ectopic ACTH syndrome; PNETs; PiNETS
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Endocrine System Diseases; Disease; Digestive System Neoplasms; Endocrine Gland Neoplasms; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Pancreatic Diseases; Paraneoplastic Syndromes; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Paraneoplastic Endocrine Syndromes; ACTH-Secreting Pituitary Adenoma; Neoplasms; Syndrome; Pituitary Neoplasms; Pituitary Diseases; Pancreatic Neoplasms; Cushing Syndrome; ACTH Syndrome, Ectopic; Nelson Syndrome; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pasireotide
• Other Study ID Numbers: CSOM230D2203; 2008-007348-32 (EudraCT Number)