Overview

This trial is active, not recruiting.

Conditions carcinoid tumor, malignant carcinoid syndrome
Treatments octreotide, placebo, everolimus
Phase phase 3
Targets mTOR, FKBP-12
Sponsor Novartis Pharmaceuticals
Start date December 2006
End date June 2017
Trial size 427 participants
Trial identifier NCT00412061, 2006-004507-18, CRAD001C2325

Summary

The purpose of this study was to evaluate whether everolimus 10 mg / day added to treatment with depot octreotide prolongs progression free survival compared to treatment with octreotide alone in patients with advanced carcinoid tumor.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
octreotide Sandostatin LAR® Depot
Octreotide 30 mg intramuscularly (i.m.) every 28 days.
everolimus RAD001
A 10-mg oral daily dosing regimen (two 5-mg tablets) of everolimus.
(Placebo Comparator)
Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1.
octreotide Sandostatin LAR® Depot
Octreotide 30 mg intramuscularly (i.m.) every 28 days.
placebo
A 10-mg oral daily dosing regimen (two 5-mg tablets) of matching placebo.

Primary Outcomes

Measure
Progression Free Survival (PFS) as Per Adjudicated Central Radiology Review
time frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010

Secondary Outcomes

Measure
Best Overall Response Rate as Per Adjudicated Central Radiology Review Based on Response Evaluation Criteria in Solid Tumors (RECIST)
time frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010
Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs)
time frame: From first day of treatment up to 28 days after last day of treatment in double blind (safety data collected till data cut off date i.e. 2nd April 2010)
Progression Free Survival (PFS) as Per Adjudicated Central Review by Change From Baseline Chromogranin A (CgA) and 5-hydroxyindoleacetic Acid (5-HIAA)
time frame: If elevated at baseline, evaluated every cycle visit (28 days/cycle)
Overall Survival Using Kaplan-Meier Methodology
time frame: The date of randomization to the date of death
Evaluation of Pharmacokinetics (PK)Parameters
time frame: Day 1 of every cycle (28 days/cycle) throughout the study

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion criteria: - Advanced (unresectable or metastatic) carcinoid tumor - Confirmed low-grade or intermediate-grade neuroendocrine carcinoma - Documented progression of disease within 12 months prior to randomization. - Measurable disease determined by triphasic computer tomography (CT) scan or magnetic resonance imaging (MRI). Exclusion criteria: - Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoma, or small cell carcinoma. - Hepatic artery embolization within the last 6 months or cryoablation of hepatic metastasis within 2 months of enrollment. - Previous treatment with mammalian target of rapamycin (mTOR) inhibitors (sirolimus, temsirolimus, everolimus) - Intolerance or hypersensitivity to octreotide, everolimus, or other rapamycins. - Severe or uncontrolled medical conditions - Chronic treatment with corticosteroids or other immunosuppressive agent. - Other primary cancer within 3 years. Other protocol-defined inclusion/exclusion criteria applied

Additional Information

Official title A Randomized, Double-blind Placebo-controlled, Multicenter Phase III Study in Patients With Advanced Carcinoid Tumor Receiving Octreotide Depot and Everolimus 10 mg/Day or Octreotide Depot and Placebo
Trial information was received from ClinicalTrials.gov and was last updated in March 2014.
Information provided to ClinicalTrials.gov by Novartis.