Sapanisertib in Treating Patients With Metastatic or Refractory Pancreatic Neuroendocrine Tumor That Cannot Be Removed by Surgery

Inclusion Criteria

• Patients must have unresectable or metastatic, histologically confirmed low or intermediate grade (Klimstra Criteria) pancreatic neuroendocrine tumor (PNET) with radiological evidence of disease progression since last treatment
• Refractory disease to treatment with an mTOR inhibitor
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
• Disease that is currently not amenable to surgery, radiation, or combined modality therapy with curative intent
• Patients must not have poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma
• Patients must have measurable disease
• Documented radiological evidence for disease progression (measurable or nonmeasurable) = = 3,000/mm^3 (within less than or equal to 14 days prior to registration)
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within less than or equal to 14 days prior to registration)
• Hemoglobin >= 10 g/dL (within less than or equal to 14 days prior to registration)
• Platelets >= 100 x 10^9/L (within less than or equal to 14 days prior to registration)
• Total serum bilirubin = = 60 ml/min (within less than or equal to 14 days prior to registration)
• NOTE: Creatinine clearance must be calculated using the Cockcroft-Gault equation
• Glycosylated hemoglobin (HbA1c) = 3 months before the first dose of study drug
• No hemorrhage after treatment
• Off-treatment with dexamethasone for 4 weeks before administration of the first dose of TAK-228
• No ongoing requirement for dexamethasone or anti-epileptic drugs
• Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care

Exclusion Criteria

• Patient is INELIGIBLE if patient discontinued prior mTOR inhibitor due to toxicity
• Patients must NOT have radiotherapy, or major surgery or active drug therapy for pNET (SSA permitted) within 4 weeks prior to study treatment start
• Patient must NOT have had previous treatment with any PI3K or AKT inhibitor
• NO hepatic artery embolization or cryoablation/radiofrequency ablation of hepatic metastasis within 2 months of study treatment start
• Patients must NOT have previous or concurrent malignancy within 2 years; exceptions are made for patients who meet any of the following conditions:
• Adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer OR
• Adequately treated stage I or II cancer currently in complete remission, or any other cancer that has been in complete remission for at least 2 years
• No more than 3 prior systemic treatment regimens for advanced PNET
• Patients with a history of the following within = 180 mm Hg, diastolic blood pressure > 95 mm Hg); use of anti-hypertensive agents to control hypertension before cycle1 day 1 is allowed
• Pulmonary hypertension
• Uncontrolled asthma or oxygen (O2) saturation 480 milliseconds, or history of congenital long
• Patients with known manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128 (TAK-228) are INELIGIBLE
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are INELGIBLE because of the potential for pharmacokinetic interactions with MLN0128 (TAK-228)
• NO treatment with strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4, or CYP2C19 within 1 week preceding the first dose of study drug
• NO patients receiving systemic corticosteroids (either intravenous [IV] or oral steroids, excluding inhalers or low-dose