Efficacy and Safety of Pasireotide Long Acting Release vs. Octreotide Long Acting Release in Patients With Metastatic Carcinoid Disease

A Multicenter, Randomized, Blinded Efficacy and Safety Study of Pasireotide LAR vs Octreotide LAR in Patients With Metastatic Carcinoid Tumors Whose Disease-related Symptoms Are Inadequately Controlled by Somatostatin Analogues.

The purpose of this randomized, multicenter, Phase III study was to compare the efficacy of paseriotide LAR and octreotide LAR in patients whose disease-related symptoms are inadequately controlled by currently available somatostatin analogues.

Study Overview

• Status: Completed
• Conditions: Symptomatic Refractory Resistant Carcinoid Disease
• Intervention / Treatment: Drug: Pasireotide; Drug: Octreotide

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426ANZ
    • Novartis Investigative Site
  • Buenos Aires, Argentina, C1264AAA
    • Novartis Investigative Site
• Austria
  • Graz, Austria, 8036
    • Novartis Investigative Site
  • Salzburg, Austria, 5020
    • Novartis Investigative Site
  • Vienna, Austria, A-1090
    • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Gent, Belgium, 9000
    • Novartis Investigative Site
• Brazil
  • CE
    • Fortaleza, CE, Brazil, 60430-370
      • Novartis Investigative Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Novartis Investigative Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Novartis Investigative Site
• France
  • Clichy, France, 92110
    • Novartis Investigative Site
  • Dijon, France, 21079
    • Novartis Investigative Site
  • Lyon, France, 69437
    • Novartis Investigative Site
  • Marseille cedex 05, France, 13385
    • Novartis Investigative Site
  • Montpellier cedex 5, France, 34295
    • Novartis Investigative Site
  • Nice Cedex, France, 06202
    • Novartis Investigative Site
  • Strasbourg, France, 67098
    • Novartis Investigative Site
• Germany
  • Bad Berka, Germany, 99438
    • Novartis Investigative Site
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Berlin, Germany, 12200
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Mainz, Germany, D-55101
    • Novartis Investigative Site
  • München, Germany, 80336
    • Novartis Investigative Site
• Israel
  • Jerusalem, Israel, 91120
    • Novartis Investigative Site
• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
    • Milano, MI, Italy, 20132
      • Novartis Investigative Site
    • Milano, MI, Italy, 20141
      • Novartis Investigative Site
  • MO
    • Modena, MO, Italy, 41100
      • Novartis Investigative Site
  • PG
    • Perugia, PG, Italy, 06100
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00168
      • Novartis Investigative Site
  • TO
    • Orbassano, TO, Italy, 10043
      • Novartis Investigative Site
• Norway
  • Tromsø, Norway, 9038
    • Novartis Investigative Site
  • Trondheim, Norway, N-7006
    • Novartis Investigative Site
• Poland
  • Gdansk, Poland, 80-958
    • Novartis Investigative Site
  • Slaskie
    • Gliwice, Slaskie, Poland, 44-101
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169610
    • Novartis Investigative Site
• Spain
  • Cataluña
    • Hospitalet de Llobregat, Cataluña, Spain, 08907
      • Novartis Investigative Site
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
• Sweden
  • Jönköping, Sweden, SE-551 85
    • Novartis Investigative Site
  • Linköping, Sweden, SE-581 85
    • Novartis Investigative Site
  • Lund, Sweden, SE-221 85
    • Novartis Investigative Site
  • Stockholm, Sweden, SE-171 76
    • Novartis Investigative Site
  • Stockholm, Sweden, SE-141 86
    • Novartis Investigative Site
  • Uppsala, Sweden, SE-751 85
    • Novartis Investigative Site
• United Kingdom
  • Basingstoke, United Kingdom, RG24 9NA
    • Novartis Investigative Site
  • Birmingham, United Kingdom, B15 2TH
    • Novartis Investigative Site
  • Glasgow, United Kingdom, G12 0YN
    • Novartis Investigative Site
  • London, United Kingdom
    • Novartis Investigative Site
  • Greater Manchester
    • Withington, Greater Manchester, United Kingdom, M20 4BX
      • Novartis Investigative Site
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2JF
      • Novartis Investigative Site
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Healthcare/TGen Clinical Research Service TGen Clinical Research Service
    • Tucson, Arizona, United States, 85724
      • University of Arizona / Arizona Cancer Center
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Dept. of Loma Linda CancerCent
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center Cedars Sinai 4
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center/University of South Florida Dept of H. Lee Moffit
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center MMC
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine Study Coordinator
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center Dept. of Duke Cancer Center(2)
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States
      • St. Luke's Hospital and Health Network St. Luke's Cancer Network
  • Texas
    • Houston, Texas, United States, 77030-4009
      • MD Anderson Cancer Center/University of Texas Dept. of MD Anderson (9)

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 or female patients aged 18 or greater
• Patients with carcinoid tumors and symptoms (diarrhea and flushing) that are not adequately controlled by somatostatin analogues.
• Female patients of child bearing potential must have a negative pregnancy test at baseline.
• Patients for whom written informed consent to participate in the study has been obtained.

Exclusion criteria:

• Patients receiving radiolabeled somatostatin analogue therapy within the 3 months or any cytotoxic chemotherapy or interferon therapy within the 4 weeks prior to randomization
• Diabetic patients on anti-diabetic medications whose fasting blood glucose is poorly controlled as indicated by HBA1C > 8%
• Patients with symptomatic cholelithiasis
• Patient with malabsorption syndrome, short bowel or cholegenic diarrhea not controlled by specific therapeutic means.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pasireotide LAR; Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed.	Drug: Pasireotide; Pasireotide LAR 60mg i.m. injection - patients may also receive pasireotide 600 µg s.c 3 times a day for symptom control as needed; Other Names: SOM230
Active Comparator: Octreotide LAR; Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed.	Drug: Octreotide; Octreotide LAR 40mg i.m. depot injection - Patients may also receive octreotide 100 µg s.c. 3 times a day for symptom control as needed; Other Names: Sadostatin LAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Achieved Clinical Symptom Improvement by Randomization Stratum and Treatment.	Percentage of patients who received clinical benefit in symptom (diarrhea and/or flushing) improvement as: Diarrhea (D)+Flushing (F): Patients with a daily mean number (#) of at least four bowel movements and a total of five or more flushing episodes. Clinical Benefit Response Criteria (CBRC): <4 daily mean bowel movements AND at least 20% reduction from Baseline in the daily mean # of bowel movements AND any reduction in the total # of flushing episodes compared with Baseline. (D) Patients with a daily mean # of at least four bowel movements and a total # of <5 flushing episodes. (CBRC) <4 daily mean bowel movements AND at least a 20% reduction from Baseline in the daily mean # of bowel movements. (F) Patients with a total # of at least 14 flushing episodes and a daily mean # of <4 bowel movements (CBRC) At least a 30% reduction from Baseline in the total # of flushing episodes.	Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in Daily Mean Number of Diarrhea Bowel Movement Episodes by Randomization Stratum and Treatment.	Percent change from Baseline in mean daily bowel movements at Month 6 were compared between the two treatment groups using ANCOVA model with treatment as the main effect and symptom levels at Baseline (e.g. mean daily bowel movement at Baseline) and randomization stratum (D+F or D) as covariates. Percentage change = (Month 6 - baseline)/baseline.	6 months
Improvement in Daily Mean Number of Flushing Episodes by Randomization Stratum and Treatment.	Percent change from Baseline in total number of flushing episodes comprising Month 6 were compared between the two treatment groups using ANCOVA model with treatment as the main effect and symptom levels at Baseline (e.g. total number of flushing episodes at Baseline) and randomization stratum (D+F or F) as covariates.	6 months
Pasireotide LAR vs. Octreotide LAR on Time to Symptom Response.		Month 6
Objective Tumor Response Rate Assessed by Investigator	Baseline evaluations were to include Triphasic CT scan or MRI of the abdomen. Triphasic CT or MRIs were to be read by same radiologist at each assessment, measuring the same target and non-target lesions and accounting for all lesions that were present at Baseline. All known disease was accounted for when assessing objective tumor status. Current objective tumor status was to be captured on Tumor Assessment CRF. Objective response rate was defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. Progression = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.	Month 6
Pasireotide LAR vs. Octreotide LAR on Disease Control Rate Based on RECIST Criteria	Disease control rate (DCR) is the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD). Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline, or a new lesion; or progression of non-target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Unknown (UNK) Progression has not been documented and one or more target lesions have not been assessed or have been assessed using a different method than baseline.	Month 6
Pasireotide LAR vs. Octreotide LAR on Quality of Life Assessed by FACIT-D Questionnaire		Month 6
Pasireotide LAR vs. Octreotide LAR on Time to Symptom Progression		Month 6
Pasireotide LAR vs. Octreotide LAR on Duration of Symptom Response		Month 6
Assess the Proportion of Patients Who Achieved at Least a 30% Reduction in Frequency of Bowel Movements		Month 6

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.
• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: May 15, 2008
• First Submitted That Met QC Criteria: June 3, 2008
• First Posted (Estimate): June 4, 2008

Study Record Updates

• Last Update Posted (Estimate): July 30, 2013
• Last Update Submitted That Met QC Criteria: June 25, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Carcinoid; neuroendocrine; somatostatin analogue; gastroenteropancreatic; Symptomatic Refractory Resistant Carcinoid Disease
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Carcinoid Tumor; Physiological Effects of Drugs; Antineoplastic Agents; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Octreotide; Pasireotide
• Other Study ID Numbers: CSOM230C2303; 2007-000739-25 (EudraCT Number)