Apatinib Combined With S-1 as Maintenance Therapy for HER-2 Negatived Gastric Cancer

Apatinib Combined With S-1 as Maintenance Therapy for HER-2 Negatived Gastric Cancer Treated With 4 Cycles Chemotherapy Valued as Stable Disease (SD)

Apatinib is a novel drug which was produced by Jiangsu Hengrui Medicine Co.Ltd in China. It is approved in advanced gastric cancer（GC）. The investigators just want to design such kind of trail to prove its effect when combined with S-1 as maintenance in advanced HER-2 negatived GC treated with 4 cycles chemotherapy and valued as SD. Investigators will evaluate progression free survival (PFS) and overall survival (OS).

Study Overview

• Status: Unknown
• Conditions: HER-2 Negatived Gastric Cancer
• Intervention / Treatment: Drug: Apatinib and S-1

Detailed Description

GC is the second most common cause of cancer-related deaths worldwide. Most patients are diagnosed with unresectable advanced or metastatic stage disease losing the radical surgery opportunity. Till now there is no novel targeted drug which can increase the OS for advanced GC patients except HER-2 positive patients.

Approximate 30 patients with unresectable GC treated with 4 cycles chemotherapy and valued as stable disease will be enrolled in this study,The investigators will evaluate the efficacy and security of apatinib and S-1 as maintenance therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yingying Huang; Phone Number: 86-10-85136715; Email: yinghh@hotmail.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Beijing Hospital
      • Contact: Yingying Huang; Phone Number: 86-10-85136715; Email: yinghh@hotmail.com

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. Histologically proved advanced HER-2 negatived gastric adenocarcinoma;
2. At least a unresectable factor before operation via CT, MRI, or PET-CT: difficult resection of locally advanced gastric cancer(T4b); hepatic metastasis (H1; at most five lesions, total diameter ≤8 cm); Peritoneal metastasis(CY1, P1) ; Definitely diagnosed as unresectable GC via exploratory laparoscopy or laparotomy;
3. ECOG performance status 0-2;
4. Age≥ 18 years old, Life expectancy estimated than 3 months;

5. For results of blood routine test and biochemical tests:

   Hgb ≥ 80g/L, WBC ≥ 4000/mm3, ANC ≥ 1.5×109/L, platelets ≥ 80×109/L ALT and AST ≤ 2.5 x upper normal limit (UNL), and ≤ 5 x UNL（Hematogenous metastases）, Serum Total bilirubin ≤ 1.5 X UNL, Serum Creatine ≤ 1.5 x UNL ；

6. Good cardiac function before the recruitment, no seizure of myocardial infarction in past half years, and controllable hypertension and other coronary heart disease;
7. Not concomitant with other uncontrollable benign disease before the recruitment(e.g. the infection in the kidney, lung and liver);
8. Informed consent.

Exclusion Criteria:

1. Subjects with poor-controlled arterial hypertension (systolic blood pressure> 140 mmHg and diastolic blood pressure > 90 mm Hg) despite standard medical management;
2. Coronary heart disease greater than Class I; I-level arrhythmia (including QT interval prolongation, for man ≥ 450 ms, for woman ≥ 470 ms) together with Class I cardiac dysfunction;
3. Patients with positive urinary protein;
4. Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction);
5. Subjects with high gastrointestinal bleeding risk, including the following conditions: local active ulcer lesions with positive fecal occult blood test (++); history of black stool, or vomiting blood in the past 2 months;
6. Contraindications include allergy to apatinib and/or its accessories, active bleeding, intestinal perforation, intestinal obstruction, within 30 days after surgery, drugs with poor-controlled hypertension, Class Ⅲ-Ⅳ cardiac dysfunction （NYHA standard）, severe hepatic and renal dysfunction（level 4）if apatinib use is considered;
7. Abnormal Coagulation (INR>1.5, APTT>1.5 UNL), with tendency of bleed;
8. Pregnant or lactating women; Any other condition that might place the patient at undue risk or preclude a patient from completing the study;
9. Treated with 4 cycles chemotherapy included Tegafur;
10. Other conditions regimented at investigators' discretion.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apatinib and S1 group; Combined with Apatinib (250mg qd po) and S-1 (40-60mg bid d1-14) as maintenance therapy in advanced HER-2 negatived GC	Drug: Apatinib and S-1; Combined with Apatinib (250mg qd po) and S-1 (40-60mg bid d1-14) as maintenance therapy in advanced HER-2 negatived GC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival	From date of registration until the date of disease progresssion or death resulting from any cause.	Patients will be followed for an average period of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	From date of registration until the date of death from any cause or the last follow-up visit.	Patients will be followed for an average period of 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year survival rate	Percentage of patients alive at 1 year.	12 months
Safety and tolerability as measured by number and grade of toxicity events	Overall Safety Profile by CTCAE V4.1	12 months

Collaborators and Investigators

• Sponsor: Beijing Hospital
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: yingying Huang, Beijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Anticipated): July 1, 2019
• Study Completion (Anticipated): July 1, 2020

Study Registration Dates

• First Submitted: November 18, 2018
• First Submitted That Met QC Criteria: May 13, 2019
• First Posted (Actual): May 15, 2019

Study Record Updates

• Last Update Posted (Actual): May 15, 2019
• Last Update Submitted That Met QC Criteria: May 13, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: 2017BJYYH-053-02

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