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

An Open Label, Stratified, Single-arm Phase II Study of Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumor (NET) After Failure of Cytotoxic Chemotherapy

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.

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.

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.