Efficacy and Safety of Anlotinib in Patients With Advanced Gastrointestinal Stromal Tumor After Failure of Imatinib: a Prospective, Single Arm and Multicenter Trial

Gastrointestinal stromal tumors (GIST) compose approximately 20% of soft tissue sarcomas with an annual incidence of approximately 7 per million population. GISTs occur throughout the GI tract, most commonly in the stomach or small intestine. The main treatment for localised GIST is surgical resection. At least 40% of these patients will develop recurrence or metastasis following complete resection. Local recurrence, liver metastases and/or dissemination within the abdominal cavity are the most common clinical manifestations. Although imatinib and sunitinib has greatly improved the quality of life and survival of patients with advanced GIST. Analysis of clinical trials revealed that patients with tumours with KIT exon 17 or 18 mutations, with a second mutation in KIT exon 17 or 18, had worse responses to imatinib and sunitinib. Some patients with PDGFRA D842V mutation do not respond to the present standard therapies.

Anlotinib (1-[[[4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinolin-7-Yl] oxy] methyl]cyclopropanamine dihydrochloride) , a multi-targeted tyrosine kinase inhibitor (TKI), characterized as a highly selective and potent c-KIT, VEGFR, PDGFR, FGFR inhibitor. In vitro and in vivo, Anlotinib has a broad spectrum of inhibitory action on tumor angiogenesis and growth, which showed broad activity against soft tissue sarcoma and GIST with D842V, D816H, V560G and V654A mutations. In 2015, the US FDA granted orphan drug treatment for ovarian cancer.

Study Overview

• Status: Unknown
• Conditions: Gastrointestinal Stromal Tumors
• Intervention / Treatment: Drug: Anlotinib

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

Contacts and Locations

• Study Contact: Name: Jian LI, PhD; Phone Number: 008613601310849; Email: oncogene@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 010
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Shen Lin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- 1. Male or female, 18 years of age or older. 2. Histologically-proven diagnosis of recurrent or metastatic GIST (Gastrointestinal Stromal Tumors).

3. Patients must have measurable disease meeting the requirement of RECIST 1.1. 4. Failure of prior treatment with imatinib or intolerant to imatinib. 5. No condition for receiving sunitinib and regorafenib. 6. ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1. Resolution of all acute toxic effects Adequate organ function. 7. The estimated survival period is more than 3 months. 8. Ability to understand and the willingness to sign a written informed consent document 9. Subject will comply with the study procedures and therapy

Exclusion Criteria:

• 1. Local or metastatic GIST is resectable. 2. Be treated with sunitinib or regorafenib. 3. AST and/or ALT > 2.5 times ULN, or Bilirubin >1.5 times upper limit of normal (ULN) 4. Neutrophil count < 1.5 x 10^9/L, or Platelet count <75 x 10^9/L, or Hemoglobin<90g/L 5. Cr >1.5×ULN 6. Other malignancy within the past 5 years except for adequately treated carcinoma in situ of the cervix or cutaneous basal cell carcinoma.

  7. Known brain metastasis, spinal cord compression, carcinomatous meningitis, or cerebral or soft meningeal disease through CT or MRI during screening stage.

  8. Within the past 1 years, subjects have one of the following disease: myocardial infarction, serious/instable angina pectoris, symptomatic congestive heart failure or cerebrovascular accident from coronary/peripheral artery bypass grafting.

  9. Known human immunodeficiency virus positivity. 10. Joining in other trail. 11. Women who are pregnant or lactating; No contraception for subject during childbearing period.

  12. Subject with other serious acute and chronic physical or mental problems, or laboratory abnormality, will increase the risks associated with trail or drug. It will also interference the judgment of the results. In the judgment of the investigator, subject is inadequate to participant the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progress Free Survival	18 month

Collaborators and Investigators

• Sponsor: Cttq
• Investigators: Principal Investigator: Xin Wu, Chinese PLA General Hospital; Principal Investigator: Xinhua Zhang, First Affiliated Hospital, Sun Yat-Sen University; Principal Investigator: Ye Zhou, Fudan University; Principal Investigator: Bo Zhang, West China Hospital; Principal Investigator: XiaoFeng Sun, Jiangsu Cancer Institute & Hospital; Principal Investigator: HongYan Qu, Harbin Medical University

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2018
• Primary Completion (Anticipated): October 30, 2019
• Study Completion (Anticipated): April 30, 2020

Study Registration Dates

• First Submitted: September 25, 2019
• First Submitted That Met QC Criteria: September 25, 2019
• First Posted (Actual): September 26, 2019

Study Record Updates

• Last Update Posted (Actual): September 26, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: 2018YJZ42

Drug and device information, study documents

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