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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00412061




Registration number
NCT00412061
Ethics application status
Date submitted
13/12/2006
Date registered
15/12/2006
Date last updated
21/11/2014

Titles & IDs
Public title
Everolimus and Octreotide in Patients With Advanced Carcinoid Tumor
Scientific 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
Secondary ID [1] 0 0
2006-004507-18
Secondary ID [2] 0 0
CRAD001C2325
Universal Trial Number (UTN)
Trial acronym
RADIANT-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoid Tumor 0 0
Malignant Carcinoid Syndrome 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Octreotide
Treatment: Drugs - Placebo
Treatment: Drugs - Everolimus

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.

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.


Treatment: Drugs: Octreotide
Octreotide 30 mg intramuscularly (i.m.) every 28 days.

Treatment: Drugs: Placebo
A 10-mg oral daily dosing regimen (two 5-mg tablets) of matching placebo.

Treatment: Drugs: Everolimus
A 10-mg oral daily dosing regimen (two 5-mg tablets) of everolimus.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) as Per Adjudicated Central Radiology Review - 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.
Timepoint [1] 0 0
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 outcome [1] 0 0
Best Overall Response Rate as Per Adjudicated Central Radiology Review Based on Response Evaluation Criteria in Solid Tumors (RECIST) - 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.
Timepoint [1] 0 0
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 outcome [2] 0 0
Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline 5-hydroxyindoleacetic Acid (5-HIAA) Level - 5-HIAA levels in urine are frequently elevated in patients with advanced carcinoid tumors. 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.
Timepoint [2] 0 0
If elevated at baseline, evaluated every cycle visit (28 days/cycle) reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010
Secondary outcome [3] 0 0
Overall Survival Using Kaplan-Meier Methodology - 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.
Timepoint [3] 0 0
Months 12, 24, 36, 48
Secondary outcome [4] 0 0
Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Double-Blind Phase) - 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.
Timepoint [4] 0 0
From first day of treatment up to 28 days after last day of treatment in double blind
Secondary outcome [5] 0 0
Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Open Label Phase) - 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.
Timepoint [5] 0 0
From first day of treatment up to 28 days after last day of treatment in double blind
Secondary outcome [6] 0 0
Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline Chromogranin A (CgA) - Serum CgA 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".
Timepoint [6] 0 0
If elevated at baseline, evaluated every cycle visit (28 days/cycle) reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010

Eligibility
Key inclusion criteria
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).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Novartis Investigative Site - Kogarah
Recruitment hospital [2] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [3] 0 0
Novartis Investigative Site - South Brisbane
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment outside Australia
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United States of America
State/province [1] 0 0
Arizona
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Arkansas
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California
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Connecticut
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Illinois
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Iowa
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Kansas
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Kentucky
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Louisiana
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Minnesota
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Missouri
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New Hampshire
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New York
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North Carolina
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Pennsylvania
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South Carolina
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Bruxelles
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Canada
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Ontario
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Canada
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Quebec
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Czech Republic
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Praha 2
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Czech Republic
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Pribram
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Finland
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Helsinki
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France
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Clichy Cédex
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France
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Lille Cedex
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France
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Montpellier
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Paris Cedex 15
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Toulouse Cedex 9
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France
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Villejuif Cedex
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Germany
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Berlin
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Germany
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Hamburg
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Athens
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Groningen
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Spain
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Madrid
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Sweden
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Uppsala
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United Kingdom
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Basingstoke

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT00412061
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications