Safety/Efficacy of Everolimus in Adults With Advanced Pancreatic Neuroendocrine Cancer Not Responsive to Chemotherapy

Brief summary public domain (ClinicalTrials.gov)

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 public domain (ClinicalTrials.gov)

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.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

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)]. Number, percentage of participants (95% Confidence Interval). Stratum 1: Everolimus 10 mg (n=115): 9.6 (4.9 to 16.5).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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]. Median, Months (95% Confidence Interval). Stratum 1: Everolimus 10 mg (n=11): 10.64 (9.79 to NA) [The upper limit was not estimable in the study as it is longer than duration of study.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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, percentage of participants (95% Confidence Interval). Stratum 2: Everolimus 10 mg + Octreotide Depot (n=45): 4.4 (0.5 to 15.1).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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, Participants. Adverse Events: Stratum 1: Everolimus 10 mg (n=115): 115. Death: Stratum 1: Everolimus 10 mg (n=115): 10. Serious Adverse Events: Stratum 1: Everolimus 10 mg (n=115): 63.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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]. Number, Participants. Adverse Events: Stratum 2: Everolimus 10 mg + Octreotide Depot (n=45): 45. Death: Stratum 2: Everolimus 10 mg + Octreotide Depot (n=45): 2. Serious Adverse Events: Stratum 2: Everolimus 10 mg + Octreotide Depot (n=45): 27.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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]. Median, Months (95% Confidence Interval). Stratum 1: Everolimus 10 mg (n=115): 9.69 (8.25 to 13.31).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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]. Median, Months (95% Confidence Interval). Stratum 2: Everolimus 10 mg + Octreotide Depot (n=45): 16.69 (11.07 to NA) [The upper limit was not estimable in the study as it is longer than duration of study.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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]. Median, months (95% Confidence Interval). Stratum 1: Everolimus 10 mg (n=115): 28.78 (20.24 to 36.37).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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]. Median, months (95% Confidence Interval). Stratum 2: Everolimus 10 mg + Octreotide Depot (n=45): 38.77 (29.08 to NA) [The upper limit was not estimable in the study as it is longer than duration of study.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Everolimus Trough Level Determination by Pharmacokinetics Parameter in Both Strata (Stratum 1 and 2) [Cycle 1 Day 15]. Mean, ng/ml (Standard Deviation). Stratum 1: Everolimus 10 mg (n=92): 15.7 (15.82); Stratum 2: Everolimus 10 mg + Octreotide Depot (n=30): 17.3 (18.08).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Effect of Octreotide Depot on the Trough Concentrations of Everolimus [Cycle 1 Day 1, Cycle 2 Day 1]. Mean, ng/ml (Standard Deviation). Cycle 1 Day 1 (pre-treatment baseline) (n=37): Stratum 2: Everolimus 10 mg + Octreotide Depot (n=38): 3.2 (2.81). Cycle 2 Day 1 (n= 38): Stratum 2: Everolimus 10 mg + Octreotide Depot (n=38): 3.7 (3.47).