Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/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
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)
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
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
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)
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)
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)
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
Sex
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
1/12/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2013
Sample size
Target
Accrual to date
Final
429
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
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Kansas
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Louisiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
New Hampshire
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
South Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Virginia
Country [22] 0 0
United States of America
State/province [22] 0 0
Washington
Country [23] 0 0
United States of America
State/province [23] 0 0
Wisconsin
Country [24] 0 0
Belgium
State/province [24] 0 0
Bruxelles
Country [25] 0 0
Canada
State/province [25] 0 0
Ontario
Country [26] 0 0
Canada
State/province [26] 0 0
Quebec
Country [27] 0 0
Czech Republic
State/province [27] 0 0
Praha 2
Country [28] 0 0
Czech Republic
State/province [28] 0 0
Pribram
Country [29] 0 0
Finland
State/province [29] 0 0
Helsinki
Country [30] 0 0
France
State/province [30] 0 0
Clichy Cédex
Country [31] 0 0
France
State/province [31] 0 0
Lille Cedex
Country [32] 0 0
France
State/province [32] 0 0
Montpellier
Country [33] 0 0
France
State/province [33] 0 0
Paris Cedex 15
Country [34] 0 0
France
State/province [34] 0 0
Strasbourg
Country [35] 0 0
France
State/province [35] 0 0
Toulouse Cedex 9
Country [36] 0 0
France
State/province [36] 0 0
Villejuif Cedex
Country [37] 0 0
Germany
State/province [37] 0 0
Berlin
Country [38] 0 0
Germany
State/province [38] 0 0
Hamburg
Country [39] 0 0
Greece
State/province [39] 0 0
Athens
Country [40] 0 0
Italy
State/province [40] 0 0
BO
Country [41] 0 0
Italy
State/province [41] 0 0
MI
Country [42] 0 0
Italy
State/province [42] 0 0
PG
Country [43] 0 0
Italy
State/province [43] 0 0
PI
Country [44] 0 0
Netherlands
State/province [44] 0 0
Groningen
Country [45] 0 0
Netherlands
State/province [45] 0 0
Rotterdam
Country [46] 0 0
Slovakia
State/province [46] 0 0
Slovak Republic
Country [47] 0 0
Spain
State/province [47] 0 0
Madrid
Country [48] 0 0
Sweden
State/province [48] 0 0
Uppsala
Country [49] 0 0
United Kingdom
State/province [49] 0 0
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/ct2/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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00412061