A Study of Anlotinib in Patients With Gastroenteropancreatic Neuroendocrine Tumor G3

A Single Group, Open Label, Multi-center Clinical Trial to Assess the Efficacy and Safety of Anlotinib in Patients With Gastroenteropancreatic Neuroendocrine Tumor G3

To assess the primary effects and safety of Anlotinib in patients with Gastroenteropancreatic Neuroendocrine Tumor G3.

Study Overview

• Status: Unknown
• Conditions: Gastroenteropancreatic Neuroendocrine Tumor G3
• Intervention / Treatment: Drug: Anlotinib

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Yihebali Chi
      • Contact: Yihebali Chi, doctor; Phone Number: 010-67781331; Email: dryihebalichi@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients should participate in the study voluntarily and sign informed consent;
• 18-75 years old;
• Histopathological proven diagnosis of high grade (G3) advanced Gastroenteropancreatic Neuroendocrine Tumor(Unresectable locally advanced or distant Metastatic). the classification is based on the Ki-67 proliferative index >20%(WHO 2010),and Provision of qualified pathological tissue for central review;
• Progression during or after treatment with first-line systematic chemotherapy;
• At least one measurable nidus (by RECIST1.1);
• Main organs function is normal;
• Eastern Cooperative Oncology Group(ECOG) performance status(PS):0-1,Life expectancy of more than 12 weeks;
• Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device，contraceptive and condom) throughout treatment and for at least 6 months after study is stopped；the result of serum or urine pregnancy test should be negative within 7 days prior to study enrollment，and the patients required to be non-lactating；Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped;

Exclusion Criteria:

• Diagnosed with low or intermediate (G1,G2) neuroendocrine tumors, Manec, adenocarcinoma;
• Functional neuroendocrine tumors(NETs) which need to be treated with long acting somatostatin analogue(SSAs) to control disease related syndromes, such as insulinoma, gastrinoma, glucagonoma, somatostatinoma, accompanied by carcinoid syndrome, Zollinger-Ellison syndrome or other active symptoms;
• Other malignancies diagnosed within the previous 5 years, except basal cell carcinoma or cervical carcinoma in situ after radical resection；
• Have received anti-vascular endothelial growth factor（VEGF）/VEGFR targeted drugs and progressed upon these drugs；
• Patients with factors that could affect oral medication (such as dysphagia，chronic diarrhea, intestinal obstruction etc.)

• Patients with any severe and/or unable to control diseases，including：

  1. Blood pressure unable to be controlled ideally(systolic pressure≥150 mmHg，diastolic pressure≥100 mmHg);
  2. Patients with Grade 1 or higher myocardial ischemia, myocardial infarction or malignant arrhythmias(including QT≥480ms) and patients with Grade 1 or higher congestive heart failure (NYHA Classification);
  3. Patients with active or unable to control serious infections;
  4. Patients with cirrhosis, decompensated liver disease, or active hepatitis;
  5. Patients with poorly controlled diabetes (fasting blood glucose(FBG)>10mmol/L)
  6. Urine protein ≥ ++，and 24-hour urinary protein excretion>1.0g confirmed;
• Patients had surgery (except biopsy) within 28 days or the surgical incision has not fully healed before the first study drug implementation;
• Patients with brain metastasis or spinal cord compression which had not surgical and / or radiation therapy,or which had previous treatment but there is no clinical imaging evidence proving the condition is stable;
• Anti-tumor therapy was performed within 4 weeks prior to initiation of the study treatment, including but not limited to chemotherapy, radical radiotherapy, bio-targeted therapy, immunotherapy, anti-tumor treatment of traditional Chinese medicine, hepatic artery embolization, hepatic metastatic cryoablation or radiofrequency ablation surgery.Palliative radiotherapy for a bone metastasis lesion within 2 weeks prior to the initiation of the investigational treatment;
• The toxic reaction of previous anticancer treatment has not been restored to grade 0 or 1 (except hair loss);
• Patients with arterial or venous thromboembolic events occurred within 6 months, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism;
• Imaging showed tumors have involved important blood vessels or by investigators determine likely during the follow-up study and cause fatal hemorrhage;
• Patients with drug abuse history and unable to get rid of or Patients with mental disorders;
• Patients participated in other anticancer drug clinical trials within 4 weeks;
• History of immunodeficiency;
• Pregnancy(Positive detection of pregnancy before drug use)or lactation;
• Patients with concomitant diseases which could seriously endanger their own safety or could affect completion of the study according to investigators' judgment;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Anlotinib	Drug: Anlotinib; Anlotinib is followed Day 1 to day 14 by 7 days off treatment in a 21-day cycle） and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival(PFS)	From randomization，each 42 days up to progressive disease(PD) or death(up to 24 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate(ORR)	each 42 days up to intolerance the toxicity or PD (up to 24 months)
Overall survival(OS)	From randomization until death (up to 24 months)
Disease Control Rate(DCR)	each 42 days up to intolerance the toxicity or PD (up to 24 months)

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 30, 2018
• Primary Completion (ANTICIPATED): August 30, 2019
• Study Completion (ANTICIPATED): August 30, 2019

Study Registration Dates

• First Submitted: February 27, 2018
• First Submitted That Met QC Criteria: March 6, 2018
• First Posted (ACTUAL): March 8, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 11, 2018
• Last Update Submitted That Met QC Criteria: September 7, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Intestinal Diseases; Pancreatic Diseases; Stomach Neoplasms; Pancreatic Neoplasms; Neuroendocrine Tumors; Intestinal Neoplasms
• Other Study ID Numbers: ALTN-13-II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No