Everolimus and Octreotide in Patients With Advanced Carcinoid Tumor (RADIANT-2)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00412061
First received: December 13, 2006
Last updated: March 5, 2014
Last verified: March 2014

December 13, 2006
March 5, 2014
December 2006
June 2017   (final data collection date for primary outcome 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 ] [ Designated as safety issue: No ]
Progression free survival (PFS) is defined as the time from randomization to the date of first documented disease progression or death from any cause. The primary analysis of PFS was based on the independent central adjudicated assessment using Kaplan-Meier method.
Assess the clinical activity of everolimus plus octreotide as defined by progression free survival, per Response Evaluation Criteria In Solid Tumors (RECIST) criteria, in patients with advanced carcinoid tumor.
Complete list of historical versions of study NCT00412061 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
    The best overall response rate is defined as the percentage of patients having achieved confirmed Complete Response + Partial Response. Complete Response (CR) = at least two determinations of CR at least 4 weeks apart before progression. • Partial response (PR) = at least two determinations of PR or better at least 4 weeks apart before progression.
  • 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) ] [ Designated as safety issue: Yes ]
    AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
  • 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) ] [ Designated as safety issue: No ]
    Serum CgA and 5-HIAA levels in urine are frequently elevated in patients with advanced carcinoid tumors. Baseline levels of serum CgA were characterized relative to the upper limited of normal (ULN). CgA levels exceeding 2 x ULN were considered to be 'Elevated'; otherwise considered as "Non-elevated". Baseline levels of 5-HIAA in urine were defined as 'High' if they exceeded the median value, and 'Low' if they were lower than or equal to the median.
  • Overall Survival Using Kaplan-Meier Methodology [ Time Frame: The date of randomization to the date of death ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from the date of randomization to the date of death from any cause. If a patient was not known to have died, survival was censored at the date of last contact. Kaplan-Meier methodology was used to estimate the median overall survival for each treatment group.
  • Evaluation of Pharmacokinetics (PK)Parameters [ Time Frame: Day 1 of every cycle (28 days/cycle) throughout the study ] [ Designated as safety issue: No ]
    The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. The PK parameters were: area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-t last), area under the concentration time curve from time zero to time t, where t is the end of the dosing interval (AUC0-t), maximum (peak) drug concentration (Cmax), time to maximum (peak) drug concentration (tmax), and minimum (trough) drug concentration (Cmin).
  • Effect of everolimus on decreasing tumor size and related tumor endpoints (best overall response rate – complete response and partial response, response duration).
  • Effect of everolimus on overall survival.
  • Changes in tumor biomarkers caused by treatment.
  • Safety and tolerability of everolimus at 10 mg / day plus octreotide depot treatment regimen.
Not Provided
Not Provided
 
Everolimus and Octreotide in Patients With Advanced Carcinoid Tumor
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Carcinoid Tumor
  • Malignant Carcinoid Syndrome
  • Drug: Octreotide
    Octreotide 30 mg intramuscularly (i.m.) every 28 days.
    Other Name: Sandostatin LAR® Depot
  • Drug: Placebo
    A 10-mg oral daily dosing regimen (two 5-mg tablets) of matching placebo.
  • Drug: Everolimus
    A 10-mg oral daily dosing regimen (two 5-mg tablets) of everolimus.
    Other Name: RAD001
  • Experimental: Octreotide+ Everolimus
    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.
    Interventions:
    • Drug: Octreotide
    • Drug: Everolimus
  • Placebo Comparator: Octreotide+ Placebo
    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.
    Interventions:
    • Drug: Octreotide
    • Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
427
June 2017
June 2017   (final data collection date for primary outcome measure)

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

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00412061
CRAD001C2325, 2006-004507-18
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP