Apatinib Plus Irinotecan as Second-line Treatment in AGC or EGJA

A Prospective, Multicenter Clinical Study of Apatinib Plus Irinotecan as Second-line Treatment in Locally Advanced or Metastatic Gastric or Gastroesophageal Junctional Adenocarcinoma

This is a prospective, multicenter, single-group clinical study of Apatinib Plus Irinotecan as second-line treatment in locally advanced or metastatic gastric or gastroesophageal junctional adenocarcinoma.

Study Overview

• Status: Unknown
• Conditions: Metastatic Gastric Adenocarcinoma
• Intervention / Treatment: Drug: Apatinib; Drug: Irinotecan

Detailed Description

This is a prospective, multicenter, single-group clinical study of Apatinib Plus Irinotecan as second-line treatment in locally advanced or metastatic gastric or gastroesophageal junctional adenocarcinoma. Interventions: Irinotecan: 180mg/m2, ivgtt,given on the first day; Apatinib: initial dose: 250mg,oral,once a day, after meal ( try to take the medicine at the same time each day). Repeat the therapeutic schedule every 3 weeks till progressive disease or intolerable toxicities. Primary Outcome Measure: PFS. Secondary Outcome Measures: OS, ORR, DCR.

• Study Type: Interventional
• Enrollment (Anticipated): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110010
      • Recruiting
      • The First Hospital of China Medical University
      • Contact: Xiujuan Qu, PhD; Phone Number: 86-24-83282542; Email: qu_xiujuan@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age：18-70，female or male.
2. Pathologically diagnosed local advanced or metastatic stomach or gastroesophageal junction with adenocarcinoma, at least one measurable objective tumor lesion by spiral CT examination（according to RECIST 1.1）.
3. First-line application of fluorouracil-based chemotherapy failed (treatment failure definition: toxic side effects can not tolerate the progress of the disease during treatment or recurrence after treatment); Note:(1) Time of first-line treatment for subjects with advanced tumour must more than 1 cycles;(2) Adjuvant/neoadjuvant therapy was allowed; adjuvant/neoadjuvant therapy will be considered as a first-line treatment if disease recurrence during treatment or after less than 24 weeks.
4. UGT1A1*28(6/6) and *6(G/G) ,or UGT1A1*28(6/6) and *6(G/A),or UGT1A1*28(6/7) and *6(G/G).
5. ECOG performance status 0-1.
6. satisfactory main organ function，laboratory test must meet the following criteria: (1) blood routine examination standards to meet: A. HB≥90g/L; B. ANC≥1.5×109/L; C. PLT≥90×109/L; (2) biochemical tests to meet the following criteria: A. Total bilirubin≤1.5 times the upper limit of normal (ULN) B. ALT and AST≤2.5ULN; C. Serum Cr≤1ULN, endogenous creatinine clearance> 60ml/min (Cockcroft-Gault formula)
7. The international normalized ratio (INR) ≤ 1.5 and some prothrombin time (PPT or APTT) ≤ 1.5ULN within 7 days before participating.
8. Expected survival≥3 months;
9. Signed informed consent (ICF) before admission;
10. Women of childbearing age must undergo a pregnancy test (serum or urine) within 7 days prior to enrollment and have a negative result and are willing to use appropriate methods for contraception at 8 weeks after the trial and at the end of the last test. For men, contraception should be used for surgical sterilization, or agreed to use the appropriate method 8 weeks after the trial and the last given test drug.

Exclusion Criteria:

1. Hypersensitivity to apatinib, irinotecan or excipients.
2. More than one chemotherapy regimen was treated after progression of gastric cancer (except for adjuvant/neoadjuvant chemotherapy with more than 24 weeks of clearance).
3. Prior exposure to irinotecan.
4. Prior exposure to irinotecan VEGFR inhibitors, such as apotinib, sorafenib, sunitinib.
5. Another primary tumor in patients, except for: systematically treatment non-melanoma skin cancer, effectively treatment cervical carcinoma in situ, or other effectively treatment tumors wtih no recurrence for more than 5 years.
6. Anti neoplastic cytotoxic drugs, biological drugs (such as monoclonal antibodies), immunotherapy (such as interleukin 2 or interferon), or other research drugs have been use within 4 weeks before participating.
7. Uncontrolled hypertention with systolic blood pressure> 140 mmHg or diastolic blood pressure> 90 mmHg, grade I or more coronary heart disease, grade I arrhythmia (including QTc interval: male> 450 ms, female> 470 ms) and grade I cardiac insufficiency.
8. Urine routine urinary protein ≥ ++, or 24 hours urine protein ≥ 1g.
9. Any toxicity more than 1 grade(according to CTCAE) caused by previous treatment, except hair loss.
10. Occasional artery/venous thrombosis events, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism occurred within 12 months before participation;
11. Intestinal obstruction occurred 4 weeks before participation.
12. Patients who underwent major surgery 4 weeks prior to initiation of treatment. The patient must be cured from any major surgery.
13. Patients who are considered to have a greater risk of medical care due to a serious, uncontrollable disease, non-metastatic systemic disease or active, uncontrollable infection. Some examples include, but not exclusively, uncontrolled ventricular arrhythmias, recent (3 months) myocardial infarction, uncontrollable epilepsy seizures, unstable spinal cord compression, superior vena cava syndrome, HRCT tips Bilateral interstitial lung disease or any mental illness that may obstruct informed consent.
14. Immunocompromised patients, for example, serological tests suggest that human immunodeficiency virus (HIV) is positive.
15. Pregnant or lactating women.
16. Have a variety of factors that affect oral medication (such as unable to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction, etc.).
17. Patients with clear gastrointestinal bleeding tendencies. Including the following: there is black stool, hematemesis history in 2 months can not be grouped; For patient with fecal occult blood (+) and the primary tumor of the stomach tumor not surgical resected, if the center of the main investigators believe that there is possible occurrence of gastrointestinal bleeding,the patient can not be grouped.
18. Ascites or pleural effusion requiring clinical treatment of persistent.
19. A history or evidence of hereditary hemorrhagic physical or coagulopathy that increases the risk of bleeding.
20. With central nervous system metastasis with symptoms.
21. With Gilbert syndrome.
22. Participated in other drug clinical trials in four weeks.
23. Researchers believe that they are not suitable for inclusion.
24. Patients who had bone metastases and had undergone palliative radiotherapy (radiotherapy> 5% bone marrow area) within 4 weeks prior to the study.

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: Irinotecan plus apatinib; Irinotecan: 180mg/m2, ivgtt,given on the first day; Apatinib: initial dose: 250mg,oral,once a day, after meal ( try to take the medicine at the same time each day). Repeat the therapeutic schedule every 3 weeks till progressive disease or intolerable toxicities.	Drug: Apatinib; Apatinib, a novel targeted inhibitor of VEGF receptor 2 (VEGFR2).; Drug: Irinotecan; Irinotecan was used as second line treatment with AGC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival [PFS]	Progression Free Survival	5-6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival [OS]	Overall Survival	12-15 months
Objective Response Rate [ORR]	Objective Response Rate	12-15 months
Disease Control Rate [DCR]	Disease Control Rate	12-15 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Degree of Treatment-Emergent Adverse Events [Safety and Tolerability]	Incidence and Degree of Treatment-Emergent Adverse Events	12-15 months
Performance Status [WHO-ECOG]	Performance Status	12-15 months
Quality of Life [WHO-QOL]	Quality of Life	12-15 months

Collaborators and Investigators

• Sponsor: China Medical University, China
• Collaborators: General Hospital of Shenyang Military Region; Shengjing Hospital; The People's Hospital of Liaoning Province; The First Hospital of Jilin University; The Second Affiliated Hospital of Harbin Medical University; Liaoning Tumor Hospital & Institute; The First Affiliated Hospital of Dalian Medical University; The Second Affiliated Hospital of Dalian Medical University; The Affiliated Tumor Hospital of Harbin Medical University; Anshan Tumor Hospital; Benxi Cental Hospital; Liaoyang Central Hospital; Panjin Central Hospital; Jilin University Sino-Japanese Friendship Hospital; Liaoyang Petrochemical General Hospital

Publications and helpful links

General Publications

• Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4. Erratum In: CA Cancer J Clin. 2011 Mar-Apr;61(2):134.
• Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. doi: 10.1056/NEJMoa073149.
• Catalano V, Graziano F, Santini D, D'Emidio S, Baldelli AM, Rossi D, Vincenzi B, Giordani P, Alessandroni P, Testa E, Tonini G, Catalano G. Second-line chemotherapy for patients with advanced gastric cancer: who may benefit? Br J Cancer. 2008 Nov 4;99(9):1402-7. doi: 10.1038/sj.bjc.6604732.
• Li J, Qin S, Xu J, Guo W, Xiong J, Bai Y, Sun G, Yang Y, Wang L, Xu N, Cheng Y, Wang Z, Zheng L, Tao M, Zhu X, Ji D, Liu X, Yu H. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol. 2013 Sep 10;31(26):3219-25. doi: 10.1200/JCO.2013.48.8585. Epub 2013 Aug 5.
• Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. doi: 10.1016/j.ejca.2011.06.002.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 5, 2017
• Primary Completion (ANTICIPATED): March 1, 2020
• Study Completion (ANTICIPATED): September 1, 2020

Study Registration Dates

• First Submitted: April 12, 2017
• First Submitted That Met QC Criteria: April 14, 2017
• First Posted (ACTUAL): April 17, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 13, 2019
• Last Update Submitted That Met QC Criteria: November 9, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Apatinib; Irinotecan; Second-line; Metastatic Gastric Adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Protein Kinase Inhibitors; Topoisomerase I Inhibitors; Irinotecan; Apatinib
• Other Study ID Numbers: CLOG0103

Drug and device information, study documents

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