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出境医 / 临床实验 / 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

Study Description
Brief Summary:
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).

Condition or disease Intervention/treatment Phase
HER-2 Negatived Gastric Cancer Drug: Apatinib and S-1 Phase 2

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 Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Apatinib Combined With S-1 as Maintenance Therapy for HER-2 Negatived Gastric Cancer Treated With 4 Cycles Chemotherapy Valued as Stable Disease (SD)
Actual Study Start Date : July 1, 2017
Estimated Primary Completion Date : July 1, 2019
Estimated Study Completion Date : July 1, 2020
Arms and Interventions
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

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


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


Other Outcome Measures:
  1. 1-year survival rate [ Time Frame: 12 months ]
    Percentage of patients alive at 1 year.

  2. Safety and tolerability as measured by number and grade of toxicity events [ Time Frame: 12 months ]
    Overall Safety Profile by CTCAE V4.1


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations

Contacts
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Contact: Yingying Huang 86-10-85136715 yinghh@hotmail.com

Locations
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China, Beijing
Beijing Hospital Recruiting
Beijing, Beijing, China, 100730
Contact: Yingying Huang    86-10-85136715    yinghh@hotmail.com   
Sponsors and Collaborators
Beijing Hospital
Jiangsu HengRui Medicine Co., Ltd.
Investigators
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Principal Investigator: yingying Huang Beijing Hospital
Tracking Information
First Submitted Date  ICMJE November 18, 2018
First Posted Date  ICMJE May 15, 2019
Last Update Posted Date May 15, 2019
Actual Study Start Date  ICMJE July 1, 2017
Estimated Primary Completion Date July 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 13, 2019)
progression-free survival [ Time Frame: Patients will be followed for an average period of 1 year ]
From date of registration until the date of disease progresssion or death resulting from any cause.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2019)
overall survival [ Time Frame: Patients will be followed for an average period of 1 year ]
From date of registration until the date of death from any cause or the last follow-up visit.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 13, 2019)
  • 1-year survival rate [ Time Frame: 12 months ]
    Percentage of patients alive at 1 year.
  • Safety and tolerability as measured by number and grade of toxicity events [ Time Frame: 12 months ]
    Overall Safety Profile by CTCAE V4.1
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Apatinib Combined With S-1 as Maintenance Therapy for HER-2 Negatived Gastric Cancer
Official Title  ICMJE Apatinib Combined With S-1 as Maintenance Therapy for HER-2 Negatived Gastric Cancer Treated With 4 Cycles Chemotherapy Valued as Stable Disease (SD)
Brief Summary 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).
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HER-2 Negatived Gastric Cancer
Intervention  ICMJE 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
Study Arms  ICMJE 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
Intervention: Drug: Apatinib and S-1
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 13, 2019)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2020
Estimated Primary Completion Date July 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03950141
Other Study ID Numbers  ICMJE 2017BJYYH-053-02
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Yingying Huang, Beijing Hospital
Study Sponsor  ICMJE Beijing Hospital
Collaborators  ICMJE Jiangsu HengRui Medicine Co., Ltd.
Investigators  ICMJE
Principal Investigator: yingying Huang Beijing Hospital
PRS Account Beijing Hospital
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP