Metastatic Gastric Adenocarcinoma
Conditions
Keywords
Gastric Carcinoma, Malignant Ascites, Intraperitoneal Chemotherapy, Bevacizumab
Brief summary
The purpose of this study is to compare the efficacy of S1 plus paclitaxel (intravenous injection & intraperitoneal injection) plus bevacizumab (intraperitoneal injection) vs. S1 plus oxaliplatin intravenous injection as first-line treatment in gastric or gastroesophageal junctional adenocarcinoma with malignant ascites.
Detailed description
This is a prospective, open-label, multicenter clinical trial, to compare the efficacy of S1 plus paclitaxel (intravenous injection & intraperitoneal injection) plus bevacizumab (intraperitoneal injection) versus S1 plus oxaliplatin intravenous injection as first-line treatment in gastric or gastroesophageal junctional adenocarcinoma with malignant ascites. A total of 66 patients who are diagnosed with gastric or gastroesophageal junctional adenocarcinoma will be allocated to receive either S1 orally administration plus paclitaxel intravenous injection & intraperitoneal injection plus bevacizumab intraperitoneal injection, or to receive S1 orally administration plus oxaliplatin intravenous injection. The primary end point is ascites response rate at 6 weeks. The secondary end points include the median overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), objective response rate (ORR), puncture free survival, volume of drainage, the quality of life (QoL) and safety.
Interventions
DRUGS1
80-120 mg/day, PO, D1-14, every 21 days
DRUGPaclitaxel
20 mg/m2/day, IP, D1-3; 50 mg/m2, IV, D1; 70 mg/m2, IV, D8; every 21 days
DRUGBevacizumab
200 mg, IP, D1, every 21 days
DRUGOxaliplatin
130 mg/m2, IV, D1, every 21 days
Sponsors
China Medical University, China
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 18 years ≥ Age≤ 70 years, male or female * Pathologically confirmed adenocarcinoma of the gastric or gastro-oesophageal junction with inoperable locally advanced or recurrent and/or metastatic disease; with medium amount of malignant ascites which can be catheterized. * Diagnostic criteria for malignant ascites (meet any of the following criteria): ascites cytology positive; or imaging or pathological confirmed peritoneal metastases. * No prior anti-tumor treatment to the metastatic disease; an interval of at least 6 months from the last adjuvant chemotherapy. * Eastern Cooperative Oncology Group (ECOG) performance status( PS) score 0-1. * Normal major organ function, and laboratory tests must meet the following criteria: hemoglobin (HGB) ≥ 90 g/L, neutrophil count ≥ 1.5×109/L, platelet count ≥ 100×109/L, total bilirubin (TBil) ≤ 1.5 upper normal limitation (UNL), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 UNL, serum creatinine (Cr) ≤ 1 UNL; creatinine clearance rate (CCr) ≥ 60 ml/min (calculated using the Cockcroft-Gault equation). * International Normalized Ratio (INR) ≤ 1.5 and partial prothrombin time (PPT) or activated partial thromboplastin time (APTT) ≤ 1.5 UNL within 7 days before enrollment. * Life expectancy of at least 12 weeks * Signed informed consent (ICF) * For women of child bearing potential, a negative serum or urine pregnancy test result should be obtained with 7 days before enrollment; Women of childbearing potential and men must agree to use adequate contraception before entering the program until at least 8 weeks after the last study drug administration.
Exclusion criteria
* Known hypersensitivity or allergic to any of the study drugs, study drug classes, or excipients in the formulation. * Subject received chemotherapy to the metastatic disease (except adjuvant/neoadjuvant chemotherapy administered 24 weeks before enrollment) * Subject with other malignancies, except for non-melanoma skin cancer or in-situ cervical carcinoma under adequate treatment, or other treated malignancies without evidence of recurrent for 5 years. * Anti-tumor cytotoxic drug therapy within 14 days prior to enrollment（longer washout time interval might needed depends on drug characteristics） * Uncontrolled hypertension which cannot be reduced to normal range by antihypertensive agents \[Systolic Blood Pressure(SBP) \>140 mmHg, diastolic blood pressure (DBP) \> 90 mmHg\], coronary artery disease \> grade 1, arrhythmia \> grade 1 \[including corrected QT(QTc) interval prolongation: QTc\>450 ms for male，QTc\>470 ms for female\], grade 1 heart failure. * Proteinuria ≥ ++，or persistent proteinuria \> 1.0 g/24 hours * Presence of any toxicity ≥ grade 1 according to NCI-CTCAE except for alopecia. * Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks, cerebral hemorrhage、cerebral infarction), deep vein thrombosis and pulmonary embolism within 12 months before enrollment. * Bowel obstruction within 6 weeks before enrollment. * Surgical treatment was performed within 6 weeks before enrollment. Subject should recover from any major surgery. * Serious uncontrolled systemic illness or medical condition or uncontrolled infections, including but not limited to: uncontrollable ventricular arrhythmias, history of documented myocardial infarction within 3 months, uncontrollable epileptic dementia, unstable spinal compression, superior vena cava syndrome, extensive bilateral interstitial pulmonary disease by high-resolution computed tomography (HRCT), or any neurological or mental abnormalities which affect compliance. * Human immunodeficiency virus (HIV) positive * Pregnancy or lactation women * Cannot be orally administered medication * Subject with a tendency for gastrointestinal hemorrhage. Including: Black stool or hematemesis within 2 months; For subjects positive in occult test with unresected primary lesion, if the principle investigator in each center considers with possibility of gastrointestinal hemorrhage, the subject could not be enrolled. * Subject with malignant pleural effusion need medical intervention. * A history or evidence of hereditary hemorrhagic constitution or coagulation disorder that increases the risk of bleeding * Subjects with central nerve system metastases * Have been enrolled in other clinical trial with investigational drug treatment within the 4 weeks of start of study treatment * For subject with bone metastases, palliative radiotherapy was given 4 weeks before enrollment (radiation field \>5%). * Any other disease or condition that the investigator considers not suitable for participating in this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ascites response rate at 6 weeks | 6 weeks | response of ascites at 6 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Volume of drainage | 12 months | Volume of drainage |
| Adverse events | 12 months | Adverse events |
| TTF | 12 months | Time to treatment failure, from 1st drug administration to discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death |
| Puncture free survival | 12 months | Puncture free survival time, from the first puncture to secondary puncture |
| OS | 2 years | Overall survival, from enrollment until death from any cause |
| ORR | 12 months | Objective response rate, the proportion of patients with reduction in tumor burden of a predefined amount |
| PFS | 12 months | Progression-free survival,From 1st drug administration to the date of first progression or date of death (whichever occurs first) |
Countries
China
Contacts
Primary ContactYunpeng Liu, M.D.
Backup ContactXiujuan Qu, M.D.
Outcome results
None listed