Neuroendocrine tumors
Conditions
Interventions
Sponsors
The First Affiliated Hospital of Zhengzhou University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Adequately understand the study and voluntarily sign the Informed Consent Form; 2) Be at least 18 years old; 3) Based on central pathology review results, patients have a confirmed histologically pathology diagnosis of low- or intermediate grade (G1 or G2) advanced (unresectable or distant metastatic)NETs. 4) Have previously progressed on no more than two types of systemic anti-tumor therapy, including long-acting somatostatin analogs (SSAs), interferon, PRRT(peptide receptor radionuclide therapy), mTOR inhibitors or chemotherapy(chemotherapies were considered as one kind of regimen, regardless of medications and cycles); patients who are unable or unwilling to receive such treatments are also eligible; 5) Have measurable lesions (according to RECIST 1.1); 6) The major organs are functioning normally ;Absolute neutrophil count (ANC) of >= 1.5*10^9/L, platelet count of >= 80*10^9/L, and hemoglobin >= 90 g/L;Serum total bilirubin = 60 ml/min;International Normalized Ratio (INR) = 60 ml/min Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) >= lower limit of normal (50%); International standard ratio (INR) <= 1.5*ULN and activated partial thrombin time <= 1.5*ULN; 7) Eastern Cooperative Oncology Group performance status of 0 or 1; 8) Have expected survival of more than 12 weeks; 9) Male or females patients with reproductive potential must agree to use an effective contraceptive method, for example, double-barrier device, condom, oral or injected birth control medication or intrauterine device, during the study and within 90 days after study treatment discontinuation. All female patients are considered to be fertile, unless the patient had natural menopause or artificial menopause or sterilization (such as hysterectomy, bilateral oophorectomy or ovarian irradiation).
Exclusion criteria
Exclusion criteria: 1) High grade (G3) neuroendocrine cancer, adenocarcinoid, pancreatic islet cell carcinoma, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma; 2) Functional NETs which need to be treated with long acting SSAs to control disease related syndromes, such as insulinoma, gastrinoma, glucagonoma, somatostatinoma, ACTHoma, VIPoma, accompanied by carcinoid syndrome, Zollinger-Ellison syndrome or other active symptoms; 3) Other malignancies diagnosed within the previous 5 years, except basal cell carcinoma or cervical carcinoma in situ after radical resection; 4) Have received anti-VEGF/VEGFR targeted drugs and progressed upon these drugs; 5) Those who are known to be allergic to recombinant humanized PD-1 monoclonal antibody drugs and their components;People who are allergic to apatinib and any excipients have been advised 6) Gastrointestinal disease or condition that investigators suspect may affect drug absorption, including, but not limited to, active gastric and duodenal ulcers, ulcerative colitis and other digestive disease, gastrointestinal tumor with active bleeding, or other gastrointestinal conditions that may cause bleeding or perforation by investigator's discretion; 7) Urinalysis shows urine protein >= 2+ or 24-hour protein quantity test shows urinary protein >= 1 g; 8) Under anti-hypertension treatment, still uncontrolled hypertension, defined as: systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg; 9) History or presence of a serious hemorrhage ( > 30 ml within 3 months), hemoptysis ( >5 ml blood within 4 weeks) or a thromboembolic event (including transient ischemic attack) within 12 months; 10) Clinically significant cardiovascular disease, including but not limited to, acute myocardial infarction within 6 months prior to enrollment, severe/unstable angina pectoris or coronary artery bypass grafting, congestive heart failure according to the New York Heart Association (NYHA) classification >= 2; ventricular arrhythmias which needs drug treatment; LVEF (LVEF) = 480 msec; 12) Surgery (except biopsy) within 28 days prior to the initiation of investigational treatment or unhealed surgical incision; 18 Brain metastases and/or spinal cord compression not treated by surgery and/or radiotherapy, and with no clinical imaging evidence of disease stability; 13) Untreated or unstable central nervous system metastases, or other malignancy. 14) Anti-tumor therapy received within 4 weeks prior to the initiation of the investigational treatment, including, but not limited to, chemotherapy, radical radiotherapy, targeted therapy, immunotherapy and anti-tumor Chinese medicine treatment, hepatic chemoembolization, cryoablation and radiofrequency ablation ; 15) Toxicity from a previous anti-tumor treatment that does not return to Grade 0 or 1 (except for hair loss); 16) Imaging showed that the tumor had invaded important blood vessels or that the tumor was likely to invade important blood vessels during the follow-up study, leading to fatal hemorrhage 17) A person with a history of substance abuse who cannot be cured or has a mental disorder 18) Any clinically significant active infection, including, but not limited to, human immunodeficiency virus (HIV) infection; 19) History of clinically significant hepatic disease, including, but not limited to, known hepatitis B virus (HBV) infection with HBV DNA positive (copies >= 1*10^4/ml);
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PFS and ORR; | — |
Countries
China
Contacts
Public ContactXingya Li
The First Affiliated Hospital of Zhengzhou University
Outcome results
None listed