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

Novartis Pharmaceuticals186 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

186

Conditions

Symptomatic Refractory Resistant Carcinoid Disease

Interventions

PasireotideDRUG

Pasireotide LAR 60mg i.m. injection - patients may also receive pasireotide 600 µg s.c 3 times a day for symptom control as needed

OctreotideDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (62)

Outcomes

Primary Outcomes

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.

Time frame: Month 6

Secondary Outcomes

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.

Time frame: 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.

Time frame: 6 months

Pasireotide LAR vs. Octreotide LAR on Time to Symptom Response.

Data from ClinicalTrials.gov

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Scottsdale Healthcare/TGen Clinical Research Service TGen Clinical Research Service

Scottsdale, Arizona, United States

University of Arizona / Arizona Cancer Center

Tucson, Arizona, United States

Loma Linda University Dept. of Loma Linda CancerCent

Loma Linda, California, United States

Cedars Sinai Medical Center Cedars Sinai 4

Los Angeles, California, United States

H. Lee Moffitt Cancer Center/University of South Florida Dept of H. Lee Moffit

Tampa, Florida, United States

Mount Sinai School of Medicine Study Coordinator

New York, New York, United States

Montefiore Medical Center MMC

The Bronx, New York, United States

Duke University Medical Center Dept. of Duke Cancer Center(2)

Durham, North Carolina, United States

St. Luke's Hospital and Health Network St. Luke's Cancer Network

Bethlehem, Pennsylvania, United States

MD Anderson Cancer Center/University of Texas Dept. of MD Anderson (9)

Houston, Texas, United States

...and 52 more locations

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.

Time frame: 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.

Time frame: Month 6