Clinical trial NCT02426034: A Study of Apatinib Tablets in the Treatment of Advanced or Metastatic Gastric Cancer
Official title: Safety and Efficacy of Apatinib in Patients With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma After Failure of Two or More Lines of Chemotherapy (Ahead-G201): a Prospective, Single-arm, Multicenter, Phase IV Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Keywords: Advanced
Metastatic
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2015-04-24
Enrollment: 2004
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A large-scale single-arm phase IV study
Primary purpose: TREATMENT

Brief summary: The large-scale phase IV study aims to verify the safety and efficacy of apatinib in patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma after failure of two lines of chemotherapy. Apatinib initiated at a recommended dose of 850mg. However, the starting dose was decided by investigator's choice based on patients' condition. Dose interruption and dose reduction were allowed according to the product label. Treatment continued until disease progression, intolerable toxicity, withdrawal of informed consent, or at investigators' discretion. The primary endpoint was safety, which was assessed by recording the incidence and severity of adverse events.


Eligibility criteria: Inclusion Criteria:

1. Age: 18 to75 years old;
2. Pathologically diagnosed with advanced gastric cancer (including adenocarcinoma of the gastroesophageal junction);
3. Failure of prior therapy (during or after treatment) in patients who have received at least two prior chemotherapy regimens;
4. ECOG PS of 0-2;
5. Major organ function has to meet the following criteria:

   For results of blood routine test (without blood transfusion within 14 days):

   HB ≥ 90g / L ANC ≥ 1.5 × 109 / L PLT ≥ 80 × 109 / L

   Biochemical tests results:

   Bilirubin \<1.25 times the upper limit of normal (ULN) ALT and AST \<2.5 × ULN; liver metastases, if any, the ALT and AST\<5 × ULN Serum Cr ≤ 1 × ULN endogenous creatinine clearance\>50ml/min (Cockcroft-Gault formula)
6. An expected survival of ≥ 3 months;
7. Patient received apatinib treatment regimen at investigators' discretion;
8. Patient has to voluntarily join the study and sign the Informed Consent Form for the study;
9. Pregnancy test (serum or urine) has to be performed for woman of childbearing age within 7 days before enrolment and the test result must be negative. They shall take appropriate methods for contraception during the study until the 8th week post the last administration of study drug. For men, (previous surgical sterilization accepted), shall agree to take appropriate methods of contraception during the study until the 8th week post the last administration of study drug.

Exclusion Criteria:

1. Subjects with uncontrolled arterial hypertension (systolic blood pressure\> 140 mmHg and diastolic blood pressure \> 90 mm Hg) despite standard medical management; Grade ≥ 2 coronary heart disease; Grade ≥ 2 arrhythmia (including QT interval prolongation, for man \> 450 ms, for woman \> 470 ms), as well as Grade ≥ 2 cardiac dysfunction;
2. Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction);
3. Subjects with high gastrointestinal bleeding risk, including the following conditions: presence of active ulceration combined with a positive fecal occult blood test (++);history of hematemesis and melena within three months before enrollment; unresected primary lesion in stomach with positive fecal occult blood test (+), ulcerated gastric carcinoma with massive alimentary tract bleeding risk judged by PIs based on gastric endoscopy finding;
4. Abnormal coagulation (INR\>1.5、APTT\>1.5 UNL), with tendency of bleeding;
5. Presence of central nervous system metastases;
6. Pregnant or lactating women;
7. Other conditions regimented at investigators' discretion.

Primary outcomes:
measure: Safety, which was assessed by recording the incidence and severity of adverse events
timeFrame: between first dose of apatinib and up to 30 days after the last dose of apatinib
Secondary outcomes:
measure: Overall Survival
timeFrame: Event driven, an expected average of 34 weeks
measure: Progression Free Survival
timeFrame: An expected average of 12 weeks
measure: Objective Response Rate
timeFrame: An expected average of 12 weeks
measure: Disease Control Rate
timeFrame: An expected average of 12 weeks
measure: Quality of life, measured by the questionnaire of EORTC QLQ-C30
timeFrame: Quality of life will be assessed at baseline (after the patients provided written informed consent) until at least 4 weeks after the last dose of study drug was administered, an expected average of 14 weeks
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjin Military 81 Hosiptal
state: Jiangsu
city: Shanghai
country: China
facility: Fudan University cancer hospital
state: Shanghai
Study officials:
affiliation: Fudan University
name: Jin Li, MD
role: PRINCIPAL_INVESTIGATOR
References: