Cabozantinib and Lanreotide as Treatment for Gastroenteropancreatic Neuroendocrine Tumors

Inclusion Criteria: 1. Pathologically confirmed G1 or G2 NET of GEP origin with locally advanced or metastatic stage who failed to one line or more than one line of small molecular kinase inhibitor (mTOR inhibitor or other targeted kinase inhibitor) or W-D G3 NET of GEP origin with locally advanced or metastatic stage who failed to one line or more than one line of chemotherapy or small molecule kinase inhibitor. 2. Radiologic progression within 12 months of entry 3. Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy. 4. Age≥ 20 years old and ECOG Performance Status ≤ 1. 5. Adequate organ and marrow function, based upon meeting all the following laboratory criteria within 14 days before first dose of study treatment: 1. Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony- stimulating factor support. 2. White blood cell count ≥ 2500/µL. 3. Platelets ≥ 100,000/µL without transfusion. 4. Hemoglobin ≥ 9 g/dL (≥ 90 g/L). 5. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). If there is liver metastasis, AST, ALT ≤ 5 x ULN. ALP ≤ 5 x ULN with documented bone metastases. 6. Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN). 7. Serum albumin ≥ 2.8 g/dl 8. (PT)/INR or partial thromboplastin time (PTT) test \< 1.3 x the laboratory ULN 9. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation: Males: (140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72) Females: \[(140 - age) x weight (kg)/(serum creatinine \[mg/dL\] ×72)\] × 0.85 10. Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g 6. At least one measurable lesion according to RECIST 1.1 over non-locally treated site, such as RT, TAE (TACE), or RFA. 7. Life expectancy greater than 12 weeks. 8. Capable of understanding and complying with the protocol requirements and must have signed informed consent document. 9. Female subjects of childbearing potential (i.e. less than or equal to 2 years post-menopause and not surgically sterile) and their partners must agree to use highly effective methods of contraception (that alone or in combination result in a failure rate of less than 1% per year when used consistently and correctly during the course of the study and for 4 months after the last dose of study treatment. \* Effective methods of birth control include: * Hormonal contraception (oral, injectable, implantable, transdermal) plus a barrier method; * intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) plus a barrier method; * bilateral tubal occlusion (females); * vasectomized partner (males). 10. Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \< 55 years-of-age must have a serum follicle stimulating (FSH) level \> 40 mIU/mL to confirm menopause). Note: Documentation may include review of medical records, medical examinations, or medical history interview by study site. Exclusion Criteria: 1. Prior use of cabozantinib. (prior use of lanreotide is acceptable) 2. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks or 5 half-lives of the agent, whichever is longer, before first dose of study treatment. 3. Receipt of any type of anticancer antibody (including investigational antibody) or systemic chemotherapy within 4 weeks before first dose of study treatment. 4. Receipt of radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible. 5. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment. 6. Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following: 1. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH). 2. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor. 7. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: a. Cardiovascular disorders: 1. Congestive heart failure Ne