Overview

Efficacy and Safety of Apatinib Combined With S-1 for Patients With Advance Gastric Cancer

Status:
Completed
Trial end date:
2020-01-31
Target enrollment:
0
Participant gender:
All
Summary
This is a single-arm, interventional study aimed to observe the efficacy and safety of Apatinib combined with S-1 for patients with advanced gastric cancer refractory to oxaliplatin plus capecitabine combination therapy
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Beijing Friendship Hospital
Treatments:
Apatinib
Criteria
Inclusion Criteria Each patient must meet the following criteria to be enrolled in this
study.

- The patient has provided signed informed consent and is amenable to compliance with
protocol schedules and testing.

- The patient is at least 18 years of age (or of an acceptable age according to local
regulations, whichever is older).

- The patient has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of
0 -2 at study entry.

- The patient has a histopathologically or cytologically confirmed diagnosis of gastric
or gastroesophageal junction (GEJ) adenocarcinoma.

- The patient has metastatic disease or locally advanced, unresectable or recurrent
disease.

- The patient has experienced documented objective radiographic or clinical disease
progression (eg, any new or worsening malignant effusion documented by ultrasound
examination) which may be confirmed by pathologic criteria (histology and/or cytology)
if appropriate, during first-line therapy, or within 6 months after the last dose of
first-line therapy with Oxaliplatin plus Capecitabine doublet with or without
anthracycline (epirubicin or doxorubicin) for unresectable or metastatic disease.

- The patient has resolution to Grade ≤1 by the National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03, of all clinically
significant toxic effects of prior locoregional therapy, surgery, or other anticancer
therapy.

- The patient has adequate organ function, defined as:

1. Total bilirubin ≤1.5 times upper limit of normal value (ULN), aspartate
transaminase (AST) and alanine transaminase (ALT) ≤3 ULN for ALT/AST if no liver
metastases, <5 ULN if liver metastases;

2. Serum creatinine ≤1.5 ULN or calculated creatinine clearance (per the
Cockcroft-Gault formula or equivalent and/or 24-hour urine collection) ≥50
mL/min;

3. Absolute neutrophil count (ANC) ≥1.5 109 /L, hemoglobin ≥ 9 g/dL (5.58 mmol/L;
packed red blood cell transfusions are not allowed within one week prior to
baseline hematology profile), and platelets ≥100 109 /L;

4. International Normalized Ratio (INR) ≤ 1.5 or Prothrombin time (PT) ≤1.5 ULN;

5. Partial thromboplastin time (PTT/APTT) ≤ 1.5 ULN.

- The patient's urinary protein is ≤1+ on dipstick or routine urinalysis. If urine
dipstick or routine analysis indicates proteinuria ≥2+, then a 24-hour urine must be
collected and must demonstrate <1000 mg of protein in 24 hours to allow participation
in the study.

- The patient, if female, is surgically sterile, postmenopausal, or compliant with a
highly effective contraceptive method (failure rate <1%) during and for 12 weeks after
the treatment period (oral hormonal contraception alone is not considered highly
effective and must be used in combination with a barrier method). If male, the patient
is surgically sterile or compliant with a highly effective contraceptive regimen
during and for 6 months after the treatment period. The label requirements with regard
to the methods and duration of contraception during and after treatment with
paclitaxel can differ between countries. Country specific requirements will apply only
if they are more stringent than those already stipulated in the protocol.

Exclusion Criteria Patients who meet any of the following criteria will be excluded from
the study.

- The patient has squamous cell or undifferentiated gastric cancer.

- The patient has undergone major surgery within 28 days prior to medications, or
central venous access device placement within 7 days prior to medications.

- The patient has received any chemotherapy other than Oxaliplatin plus Capecitabine for
advanced gastric or GEJ adenocarcinoma.

- The patient has received previous systemic chemotherapy with a cumulative dose of >900
mg/m2 of epirubicin or >400 mg/m2 of doxorubicin.

- The patient has received any previous systemic therapy (including investigational
agents) targeting vascular endothelial growth factor(VEGF) or the vascular endothelial
growth factor receptor(VEGFR) signaling pathways. Other previous targeted therapies
are permitted, if stopped at least 28 days prior to randomization.

- The patient has a history of deep vein thrombosis, pulmonary embolism, or any other
significant thromboembolism (venous port or catheter thrombosis or superficial venous
thrombosis are not considered "significant") during the 3 months prior to
randomization.

- The patient is receiving therapeutic anticoagulation with warfarin, low-molecular
weight heparin or similar agents. Patients receiving prophylactic, low-dose
anticoagulation therapy are eligible provided that the coagulation parameters defined
in the inclusion criteria (INR ≤1.5 and PTT/APTT ≤1.5 ULN) or (PT ≤1.5 ULN and
PTT/aPTT ≤1.5 ULN) are met.

- The patient is receiving chronic therapy with nonsteroidal anti-inflammatory agents
(NSAIDs, eg, indomethacin, ibuprofen, naproxen or similar agents) or other
anti-platelet agents (eg, clopidogrel, ticlopidine, dipyridamole, anagrelide). Aspirin
use at doses up to 325 mg/day is permitted.

- The patient has significant bleeding disorders, vasculitis, or had a significant
bleeding episode from the gastrointestinal tract within 3 months prior to study entry.

- History of gastrointestinal perforation and/or fistulae within 6 months prior to
medications.

- The patient has symptomatic congestive heart failure (New York Heart Association
II-IV) or symptomatic or poorly controlled cardiac arrhythmia.

- The patient has experienced any arterial thrombotic event, including myocardial
infarction, unstable angina, cerebrovascular accident, or transient ischemic attack,
within 6 months prior to randomization.

- The patient has uncontrolled arterial hypertension ≥150/≥90 mm Hg despite standard
medical management.

- The patient has a serious or non healing wound or peptic ulcer or bone fracture within
28 days prior to medications.

- The patient has a bowel obstruction, history or presence of inflammatory enteropathy
or extensive intestinal resection (hemicolectomy or extensive small intestine
resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic
diarrhea.

- The patient has a serious illness or medical condition(s) including, but not limited
to the following:

1. Known human immunodeficiency virus infection or acquired immunodeficiency
syndrome-related illness;

2. Active or uncontrolled clinically serious infection;

3. Previous or concurrent malignancy except for basal or squamous cell skin cancer
and/or in situ carcinoma of the cervix, or other solid tumors treated curatively
and without evidence of recurrence for at least 3 years prior to the study;

4. Uncontrolled metabolic disorders or other nonmalignant organ or systemic diseases
or secondary effects of cancer that induce a high medical risk and/or make
assessment of survival uncertain;

5. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
study drug administration, or may interfere with the interpretation of study
results, and in the judgment of the Investigator would make the patient
ineligible for entry into this study;

6. History or evidence of known central nervous system metastases or carcinomatous
meningitis;

7. Known allergy or hypersensitivity to monoclonal antibody treatment or any
components used in the apatinib;

8. Known allergy or hypersensitivity to S-1 or any components used in the S-1
preparation.

- The patient is pregnant or breastfeeding.

- The patient is currently enrolled in, or discontinued within the last 28 days from a
clinical trial involving an investigational product or non-approved use of a drug, or
concurrently enrolled in any other type of medical research judged not to be
scientifically or medically compatible with this study. Patients participating in
surveys or observational studies are eligible to participate in this study