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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00363051




Registration number
NCT00363051
Ethics application status
Date submitted
2/08/2006
Date registered
15/08/2006
Date last updated
10/05/2013

Titles & IDs
Public title
Safety/Efficacy of Everolimus in Adults With Advanced Pancreatic Neuroendocrine Cancer Not Responsive to Chemotherapy
Scientific title
An Open Label, Stratified, Single-arm Phase II Study of Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumor (NET) After Failure of Cytotoxic Chemotherapy
Secondary ID [1] 0 0
CRAD001C2239
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Islet Cell Carcinoma 0 0
Neuroendocrine Carcinoma 0 0
Neuroendocrine Tumor 0 0
Pancreatic Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Everolimus 10 mg

Experimental: Everolimus 10 mg - Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day.

Stratum 2 patients who were to receive everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot therapy.

Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.


Treatment: Drugs: Everolimus 10 mg
Participants took two 5 mg tablets of Everolimus orally with a glass of water, once daily (preferably in the morning) in a fasting state or after no more than a light, fat-free meal. Dosing was to occur at the same time each day. If vomiting occurred, the vomited dose was not to be replaced.

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

Outcomes
Primary outcome [1] 0 0
Objective Response Rate: Percentage of Participants With Best Over All Response of Complete Response or Partial Response by Central Radiology Review (Stratum 1) Based on Response Evaluation Criteria in Solid Tumors (RECIST)
Timepoint [1] 0 0
from date of randomization/start of treatment until first documented response confirmed 4 weeks later( at least 3 months)
Secondary outcome [1] 0 0
Duration of Overall Response (Stratum 1) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review
Timepoint [1] 0 0
from date of first documented confirmed response to time to progression, at least 3 months
Secondary outcome [2] 0 0
Duration of Overall Response (Stratum 2) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review
Timepoint [2] 0 0
from date of first documented confirmed response to time to progression, at least 3 months
Secondary outcome [3] 0 0
Objective Response Rate: Percentage of Participants With Best Over All Response of Complete Response or Partial Response by Central Radiology Review (Stratum 2) Based on Response Evaluation Criteria in Solid Tumors (RECIST)
Timepoint [3] 0 0
from date of randomization/start of treatment until first documented response confirmed 4 weeks later (at least 3 months)
Secondary outcome [4] 0 0
Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs)[Stratum 1]
Timepoint [4] 0 0
on or after the day of the first intake of study treatment to starting no later than 28 days after study treatment discontinuation, at least every month
Secondary outcome [5] 0 0
Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs) [Stratum 2]
Timepoint [5] 0 0
on or after the day of the first intake of study treatment to starting no later than 28 days after study treatment discontinuation, at least every month
Secondary outcome [6] 0 0
Time to Progression Free Survival (PFS) Per Central Radiology Review (Stratum 1)
Timepoint [6] 0 0
from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 September 2010
Secondary outcome [7] 0 0
Time to Progression Free Survival (PFS) Per Central Radiology Review (Stratum 2)
Timepoint [7] 0 0
from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 September 2010
Secondary outcome [8] 0 0
Time to Overall Survival (OS)(Stratum 1)
Timepoint [8] 0 0
from randomisation to dates of disease progression, death from any cause, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 April 2012
Secondary outcome [9] 0 0
Time to Overall Survival (OS) (Stratum 2)
Timepoint [9] 0 0
from randomisation to dates of disease progression, death from any cause, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 April 2012
Secondary outcome [10] 0 0
Everolimus Trough Level Determination by Pharmacokinetics Parameter in Both Strata (Stratum 1 and 2)
Timepoint [10] 0 0
Cycle 1 Day 15
Secondary outcome [11] 0 0
Effect of Octreotide Depot on the Trough Concentrations of Everolimus
Timepoint [11] 0 0
Cycle 1 Day 1, Cycle 2 Day 1

Eligibility
Key inclusion criteria
Inclusion criteria for both strata:

* Advanced (unresectable or metastatic) biopsy-proven pancreatic Neuroendocrine tumor (NET)
* Confirmed low-grade or intermediate-grade neuroendocrine carcinoma
* Objective disease progression by Response Evaluation Criteria in Solid tumors (RECIST) criteria while receiving cytotoxic chemotherapy or at any time after receiving an adequate course of cytotoxic chemotherapy (i.e., at least 3 consecutive cycles or months of treatment with the same cytotoxic drug or regimen)
* Presence of at least one measurable disease using RECIST criteria at screening (computer tomography [CT] or Magnetic resonance imaging [MRI])
* Adequate bone marrow, liver and kidney function
* WHO Performance Status 0-2.

Inclusion criteria for Stratum 2 only:

* Meet all inclusion criteria defined above for both strata.
* Receiving treatment (at least 3 consecutive months) with Octreotide Depot.
* In addition to documentation of progressive disease on or after chemotherapy, patients in stratum 2 must have documented objective progression of disease while receiving Octreotide Depot.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria for both strata:

* Anticancer therapy within 3 weeks of enrollment.
* Patients with poorly differentiated neuroendocrine carcinoma
* Hepatic artery embolization within the last 6 months
* Prior therapy with everolimus or other rapamycins (sirolimus, temsirolimus)
* Other concurrent malignancy
* Other serious intercurrent infections or nonmalignant uncontrolled medical illnesses

Exclusion Criterion for Stratum 1 only:

• Received treatment with Octreotide Depot or any other long-acting somatostatin analogue in the 60 days prior to enrollment or any short-acting somatostatin analogue in the two weeks prior to enrollment.

Other protocol-defined inclusion/exclusion criteria applied.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
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)
Recruitment hospital [1] 0 0
Novartis Investigative Site - Heidelberg
Recruitment hospital [2] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [3] 0 0
Novartis Investigative Site - Kogarah
Recruitment postcode(s) [1] 0 0
- Heidelberg
Recruitment postcode(s) [2] 0 0
- Herston
Recruitment postcode(s) [3] 0 0
- Kogarah
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
New Hampshire
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Wisconsin
Country [16] 0 0
Argentina
State/province [16] 0 0
Buenos Aires
Country [17] 0 0
Argentina
State/province [17] 0 0
Santa Fe
Country [18] 0 0
Belgium
State/province [18] 0 0
Leuven
Country [19] 0 0
Canada
State/province [19] 0 0
British Columbia
Country [20] 0 0
Canada
State/province [20] 0 0
Nova Scotia
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
France
State/province [23] 0 0
Billancourt
Country [24] 0 0
France
State/province [24] 0 0
Clichy Cedex
Country [25] 0 0
France
State/province [25] 0 0
Lyon Cedex
Country [26] 0 0
France
State/province [26] 0 0
Reims
Country [27] 0 0
France
State/province [27] 0 0
Toulouse
Country [28] 0 0
France
State/province [28] 0 0
Villejuif Cedex
Country [29] 0 0
Germany
State/province [29] 0 0
Berlin
Country [30] 0 0
Germany
State/province [30] 0 0
Erlangen
Country [31] 0 0
Germany
State/province [31] 0 0
Essen
Country [32] 0 0
Germany
State/province [32] 0 0
Frankfurt
Country [33] 0 0
Germany
State/province [33] 0 0
Heidelberg
Country [34] 0 0
Germany
State/province [34] 0 0
Marburg
Country [35] 0 0
Germany
State/province [35] 0 0
Ulm
Country [36] 0 0
Italy
State/province [36] 0 0
Milano
Country [37] 0 0
Italy
State/province [37] 0 0
Modena
Country [38] 0 0
Italy
State/province [38] 0 0
Pisa
Country [39] 0 0
Italy
State/province [39] 0 0
Rome
Country [40] 0 0
Italy
State/province [40] 0 0
Torrette di Ancona
Country [41] 0 0
Netherlands
State/province [41] 0 0
Gronigen
Country [42] 0 0
Spain
State/province [42] 0 0
Barcelona
Country [43] 0 0
Spain
State/province [43] 0 0
L'Hospitalet de Llobregat
Country [44] 0 0
Spain
State/province [44] 0 0
Madrid
Country [45] 0 0
Sweden
State/province [45] 0 0
Uppsala

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.