An Open Label, Stratified, Single-arm Phase II Study of Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumor (NET) After Failure of Cytotoxic Chemotherapy
Overview
- Phase
- Phase 2
- Intervention
- Everolimus 10 mg
- Conditions
- Islet Cell Carcinoma
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 160
- Locations
- 21
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: 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.
Intervention: Octreotide Depot
Outcomes
Primary Outcomes
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)
Time Frame: 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 Outcomes
- 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 (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)
- 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)(from date of randomization/start of treatment until first documented response confirmed 4 weeks later (at least 3 months))
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Everolimus Trough Level Determination by Pharmacokinetics Parameter in Both Strata (Stratum 1 and 2)(Cycle 1 Day 15)
- Effect of Octreotide Depot on the Trough Concentrations of Everolimus(Cycle 1 Day 1, Cycle 2 Day 1)