Safety/Efficacy of Everolimus in Adults With Advanced Pancreatic Neuroendocrine Cancer Not Responsive to Chemotherapy
- Conditions
- Islet Cell CarcinomaNeuroendocrine CarcinomaNeuroendocrine TumorPancreatic Neoplasms
- Interventions
- Registration Number
- NCT00363051
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 160
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Everolimus 10 mg 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. Everolimus 10 mg Octreotide Depot 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.
- Primary Outcome Measures
Name Time Method 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) from date of randomization/start of treatment until first documented response confirmed 4 weeks later( at least 3 months) Objective response rate was defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. Progression = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.
- Secondary Outcome Measures
Name Time Method Duration of Overall Response (Stratum 1) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review from date of first documented confirmed response to time to progression, at least 3 months Duration of overall response applies only to patients whose best overall response was complete response (CR) or partial response (PR):
* 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.
Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesionsDuration of Overall Response (Stratum 2) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review from date of first documented confirmed response to time to progression, at least 3 months Duration of overall response applies only to patients whose best overall response was complete response (CR) or partial response (PR):
* 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.
Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesionsObjective 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) from date of randomization/start of treatment until first documented response confirmed 4 weeks later (at least 3 months) Objective response rate was defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. Progression = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.
Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs)[Stratum 1] 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 Adverse events 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. Serious adverse events 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.
Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs) [Stratum 2] 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 Adverse events 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. Serious adverse events 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.
Time to Progression Free Survival (PFS) Per Central Radiology Review (Stratum 1) 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 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 Kaplan-Meier estimate of the PFS survival function was constructed.
Median PFS was obtained and displayed along with 95% confidence intervals.Time to Progression Free Survival (PFS) Per Central Radiology Review (Stratum 2) 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 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 Kaplan-Meier estimate of the PFS survival function was constructed.
Median PFS was obtained and displayed along with 95% confidence intervals.Time to Overall Survival (OS)(Stratum 1) 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 Overall survival measures the time of survival , with any response or disease progression, until death. The OS is defined as the time from date of start of treatment to date of death due to any cause.
If a patient is not known to have died, survival was censored at the date of last contact. In each treatment stratum, the Kaplan-Meier estimate of the overall survival function was constructed.Time to Overall Survival (OS) (Stratum 2) 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 Overall survival measures the time of survival , with any response or disease progression, until death. The OS is defined as the time from date of start of treatment to date of death due to any cause.
If a patient is not known to have died, survival was censored at the date of last contact. In each treatment stratum, the Kaplan-Meier estimate of the overall survival function was constructed.Everolimus Trough Level Determination by Pharmacokinetics Parameter in Both Strata (Stratum 1 and 2) Cycle 1 Day 15 For all patients in both strata, a blood sample for everolimus trough level determination will be collected immediately prior to the everolimus administration on Cycle 1 Day 15, Cycle 2 Day 1, and every month thereafter. A treatment cycle was defined as 28 days of consecutive daily treatment with everolimus and treatment continued until tumor progression. It is critical that patients not take their daily everolimus dose before the sample is drawn.
Effect of Octreotide Depot on the Trough Concentrations of Everolimus Cycle 1 Day 1, Cycle 2 Day 1 The effect of Octreotide Depot on the trough concentrations of everolimus was assessed at Cycle 1 Day 15.
Trial Locations
- Locations (21)
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Miami
🇺🇸Miami, Florida, United States
Scott & White Memorial Hospital
🇺🇸Temple, Texas, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
The University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Cedars-Sinai Outpatient Cancer Center/Samuel Oschin Comprehensive Cancer Inst.
🇺🇸Los Angeles, California, United States
LSUHC Multispecialty Clinic
🇺🇸New Orleans, Louisiana, United States
Novartis Investigative Site
🇸🇪Uppsala, Sweden
Arthur G. James Cancer Hospital/Ohio State University
🇺🇸Columbus, Ohio, United States
M. D Anderson Cancer Center
🇺🇸Houston, Texas, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
University of Wisconsin Hospital & Clinics
🇺🇸Madison, Wisconsin, United States
USC Medical Center
🇺🇸Los Angeles, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Lynn Ratner, M.D.
🇺🇸New York, New York, United States
H. Lee Moffit Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
UCSF Comprehensive Cancer Center
🇺🇸San Francisco, California, United States