Clinical trial NCT00363051: Safety/Efficacy of Everolimus in Adults With Advanced Pancreatic Neuroendocrine Cancer Not Responsive to Chemotherapy
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Islet Cell Carcinoma
Neuroendocrine Carcinoma
Neuroendocrine Tumor
Pancreatic Neoplasms
Keywords: Pancreatic
Tumor
Islet Cell
Carcinoma
Neuroendocrine
Endocrine
Atypical Carcinoid
RADIANT1
RADIANT-1
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-08-15
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to assess the efficacy and safety of everolimus in the treatment of advanced pancreatic neuroendocrine tumor (NET) not responsive to cytotoxic chemotherapy. All patients were treated with everolimus until either tumor progression was documented using a standard criteria that measures tumor size called Response Evaluation Criteria in Solid tumors (RECIST), or until unacceptable toxicity occurred, or until the patient or investigator requested discontinuation of treatment.

Detailed description: This was a stratified two-stage, single-arm, phase 2 study of treatment with everolimus in patients with advanced (unresectable or metastatic) pancreatic neuroendocrine tumor (NET) after failure of cytotoxic chemotherapy.

Stratum 1, consisted of patients not receiving chronic Octreotide Depot therapy, will receive everolimus monotherapy at 10 mg/day.

Stratum 2, consisting of patients with tumors that have progressed during Octreotide Depot treatment will continue their entry dose of Octreotide Depot plus everolimus 10 mg/day.

Eligibility 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.

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.

Primary outcomes:
measure: 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)
timeFrame: from date of randomization/start of treatment until first documented response confirmed 4 weeks later( at least 3 months)
Secondary outcomes:
measure: Duration of Overall Response (Stratum 1) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review
timeFrame: from date of first documented confirmed response to time to progression, at least 3 months
measure: Duration of Overall Response (Stratum 2) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review
timeFrame: from date of first documented confirmed response to time to progression, at least 3 months
measure: 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)
timeFrame: from date of randomization/start of treatment until first documented response confirmed 4 weeks later (at least 3 months)
measure: Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs)[Stratum 1]
timeFrame: 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
measure: Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs) [Stratum 2]
timeFrame: 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
measure: Time to Progression Free Survival (PFS) Per Central Radiology Review (Stratum 1)
timeFrame: 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
measure: Time to Progression Free Survival (PFS) Per Central Radiology Review (Stratum 2)
timeFrame: 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
measure: Time to Overall Survival (OS)(Stratum 1)
timeFrame: 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
measure: Time to Overall Survival (OS) (Stratum 2)
timeFrame: 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
measure: Everolimus Trough Level Determination by Pharmacokinetics Parameter in Both Strata (Stratum 1 and 2)
timeFrame: Cycle 1 Day 15
measure: Effect of Octreotide Depot on the Trough Concentrations of Everolimus
timeFrame: Cycle 1 Day 1, Cycle 2 Day 1
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: USC Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Outpatient Cancer Center/Samuel Oschin Comprehensive Cancer Inst.
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffit Cancer Center & Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: New Orleans
country: United States
facility: LSUHC Multispecialty Clinic
state: Louisiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Lynn Ratner, M.D.
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital/Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Houston
country: United States
facility: M. D Anderson Cancer Center
state: Texas
city: Temple
country: United States
facility: Scott & White Memorial Hospital
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Hospital & Clinics
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Santa Fe
country: Argentina
facility: Novartis Investigative Site
city: Heidelberg
country: Australia
facility: Novartis Investigative Site
city: Herston
country: Australia
facility: Novartis Investigative Site
city: Kogarah
country: Australia
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Halifax
country: Canada
facility: Novartis Investigative Site
state: Nova Scotia
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Billancourt
country: France
facility: Novartis Investigative Site
city: Clichy Cedex
country: France
facility: Novartis Investigative Site
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Reims
country: France
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Marburg
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
city: Modena
country: Italy
facility: Novartis Investigative Site
city: Pisa
country: Italy
facility: Novartis Investigative Site
city: Rome
country: Italy
facility: Novartis Investigative Site
city: Torrette di Ancona
country: Italy
facility: Novartis Investigative Site
city: Gronigen
country: Netherlands
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: