a trial to assess efficacy, safety, pharmacokinetics of octreotide subcutaneous injection in patients with gastroentero-pancreatic neuroendocrine tumor (gep-net)

Conditions: Gastrointestinal Neuroendocrine Pancreatic Tumor

Summary: the purpose of this study is to compare the effectiveness, safety, pharmacokinetics (pk) of syhx2008 vs octreotide microspheres (sandostatin lar@) in patients with advanced, well-differentiated gep-net.

this is a phase ii, open-label randomized study to assess the pk, efficacy, and safety of syhx2008 in adult patients with well-differentiated gep-net. patients will be randomized to syhx2008 cohort or octreotide microspheres cohort (sandostatin lar@).

Eligibility criteria:
inclusion criteria: 1. male or female patient ≥18 years old; 2. histologically confirmed, advanced gep-net; 3. at least 1 measurable, somatostatin receptor-positive lesion according to recist 1.1; 4. previous treatment with ≤2 systemic antitumor drugs; 5. patients who do not have liver metastasis, with alanine aminotransferase (alt) and aspartate aminotransferase (ast) and alkaline phosphatase (alp) levels ≤ 2.5 times the upper limit of normal (uln) ; and who do have liver metastasis, with alt and ast ≤ 5 times uln; serum total bilirubin \<1.5 times the uln; absolute neutrophil count (anc) of ≥1.5×10\^9/l, platelet count of ≥90×10\^9/l, and hemoglobin ≥9 g/dl; or international normalized ratio (inr) ≤1.5 uln and activated partial thromboplastin time (aptt) ≤1.5 uln; 6. ecog performance status of 0 to 1 7. have expected survival of more than 3 months; 8. adequately understand the study and voluntarily sign the informed consent form; 9. females patients with reproductive potential must agree to use an effective contraceptive method, for example, intrauterine devices, birth control medicine or condoms, during the study and within 3 months after study treatment discontinuation; or serum pregnancy tests negative and must be non-lactating participants; or males should agree contraception during the study and for within 3 months after study treatment discontinuation. exclusion criteria: 1. uncontrolled or severe diarrhea with significant dehydration; 2. other malignancies diagnosed within the previous 5 years, except basal cell carcinoma or cervical carcinoma in situ after radical resection; 3. anti-tumor therapy received within 4 weeks prior to the initiation of the investigational treatment, for example mammalian target of rapamycin (mtor) inhibitors or multi-target tyrosine kinase inhibitors (tki); or short-acting octreotide acetate was received subcutaneously or intravenously within 1 weeks prior to the initiation of the investigational treatment; 4. interferon was received within 4 weeks prior to the initiation of the investigational treatment; or chemotherapy was received within 4 weeks prior to the initiation of the investigational treatment; or transarterial chemoembolization was received within 12 months prior to screening; or previously received peptide receptor radionuclide therapy (prrt) at any time; or received radiation therapy, anti-tumor traditional chinese medicine treatment, hepatic artery intervention embolization, liver metastasis cryoablation or radiofrequency ablation, and other systemic anti-tumor drug treatments within 4 weeks prior to the initiation of the investigational treatment; or had participated in other clinical trials within 30 days prior to screening 5. surgery (except biopsy) within 28 days prior to the initiation of investigational treatment or unhealed surgical incision; 6. glycated hemoglobin (hba1c) \> 8.5%; 7. patients have symptomatic cholelithiasis or a history of symptomatic cholelithiasis at screening, but with no performed surgery treatment; 8. patients with active brain metastases or cancerous meningitis meet any of the following criteria: a) patients with prior brain metastases, imaging within 4 weeks prior to the first use of investigational drug show progression of the original lesion, or new brain metastases; b) clinical symptoms associated with central nervous system metastasis did not recovery to baseline; c) use cortisols, radiotherapy and other drugs to control the symptoms of central nervous system metastasis within 4 weeks before the first use of the investigational drug; 9. the adverse reactions of previous antitumor therapy have not returned to ≤ grade 1 according to ctcae v5.0 (except that the investigators evaluate no safety risk, such as hair loss, grade 2 peripheral neuropathy or dysfunction); 10. any clinically significant uncontrolled neurological, gastrointestinal, renal (serum creatinine \> 1.5 uln), pulmonary, or other significant disease requiring exclusion assessed in the opinion of the investigator; 11. patients had hepatitis b virus (hbv) infection with hbv dna positive (copies ≥1×10\^4/ml or ≥2000 iu/ml); known hepatitis c antibodies positive and hcv rna higher than the lower detection limit ; or human immunodeficiency virus (hiv) positive, treponema pallidum antibody positive;. 12. a history of allergy to any excipient of the investigational drug or any similar chemical structure to the investigational drug; 13. patients had any severe or uncontrolled disease, including: 1) poor blood pressure control (systolic ≥160 mmhg or diastolic ≥100 mmhg);2) grade i or higher myocardial ischemia or myocardial infarction, symptomatic or poorly controlled arrhythmia, or congenital long qt syndrome (including qtcf ≥450ms for males, qtcf ≥470ms for females), or ≥ grade 2 congestive heart failure \[nyha classification\]; 3) serious infections that are not under control (oral or intravenous systemic anti-infection therapy is required for 2 weeks before the first use of the investigational drug, except for uncomplicated urinary tract infections and upper respiratory tract infections);4) previous or current severe bleeding (\>30ml of bleeding within 3 months), hemoptysis (\>5ml of fresh blood within 4 weeks), or thromboembolic events (including transient ischemic attacks) within 12 months; 14. other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other conditions are inappropriate for the use of the investigational product or affect interpretation of study results.