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

NCT ID: NCT04106024

Last Updated: 2019-09-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-23
• Study Completion Date: 2020-04-30

Brief Summary

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.

Conditions

Gastrointestinal Stromal Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Anlotinib

Anlotinib 12mg.qd ,taken for 2 weeks and discontinued for 1 week, namely 3 weeks (21 days).

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cttq

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xin Wu

Role: PRINCIPAL_INVESTIGATOR

Chinese PLA General Hospital

Xinhua Zhang

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital, Sun Yat-Sen University

Ye Zhou

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Bo Zhang

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

XiaoFeng Sun

Role: PRINCIPAL_INVESTIGATOR

Jiangsu Cancer Institute & Hospital

HongYan Qu

Role: PRINCIPAL_INVESTIGATOR

Harbin Medical University

Locations

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jian LI, PhD

Role: CONTACT

oncogene@163.com

008613601310849

Lin Shen

Role: CONTACT

Facility Contacts

shen lin

Role: primary

Other Identifiers

2018YJZ42

Identifier Type: -

Identifier Source: org_study_id