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In previous studies, we found that POF (A combination of oxaliplatin, fluorouracil and Paclitaxel) regimen appears to be of good efficacy and is well tolerated in patients with advanced gastric cancer. Apatinib is an orally antiangiogenic agent. It was approved and launched in China in 2014 as a 3rd-line treatment for patients with advanced gastric cancer. Therefore, investigators initialize this dose escalation phase I study to explore the safety of combination of apatinib and POF as first-line treatment for advanced gastric cancer. Investigators will analyze the maximum tolerated dose (MDT) and dose-limiting toxicity (DLT) of apatinib in this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Apatinib plus POF | Experimental | This study will include a sequential evaluation of 3 subjects per cohort. Cohort 1: apatinib 250 mg per day and POF. Cohort 2: apatinib 375 mg per day and POF. Cohort 3: apatinib 500 mg per day and POF. Cohort 4: apatinib 625 mg per day and POF. Cohort 5: apatinib 750 mg per day and POF. A dose limiting toxicity (DLT) event is defined as any of the following events in the first 4-week period:
If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Apatinib | Drug | Apatinib 250mg p.o. qd in first cohort (3 subjects). 375mg p.o. qd in second cohort (3 subjects). 500mg p.o. qd in third cohort (3 subjects). 625mg p.o. qd in forth cohort (3 subjects); 750mg p.o. qd in fifth cohort (3 subjects). Other Name: |
| Measure | Description | Time Frame |
|---|---|---|
| Dose limiting toxicity | Dose limiting toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.03 criteria | From enrollment to completion of study. Estimated about 12 months. |
| Maximum tolerance dose | Maximum tolerance dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DTL reported. | From enrollment to completion of study. Estimated about 12 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate | Clinical response of treatment according to RESIST v1.1 criteria (ORR, objective response rate). | From enrollment to 3 months after treatment |
| Progression-free survival |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rongbo Lin | Contact | 008613705919382 | rongbo_lin@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Rongbo Lin | Fujian Cancer Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rongbo Lin | Recruiting | Fuzhou | Fujian | 350014 | China |
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| ID | Term |
|---|---|
| C553458 | apatinib |
| D017239 | Paclitaxel |
| D000077150 | Oxaliplatin |
| D005472 | Fluorouracil |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
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| POF | Drug | The POF regimen consisted of a 3-hour infusion of paclitaxel (135 mg/m2) followed by oxaliplatin (85 mg/m2) and Calcium Levofolinate (200 mg/m2).Subsequently, a 46-hour infusion of fluorouracil (2400 mg/m2) was administered using an ambulatory pump, repeating the cycle every 14 days. |
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|
The length of time from enrollment until the time of progression of disease (PFS, progression-free survival).
| From enrollment to progression of disease. Estimated about 6 months. |
| Overall survival | The length of time from enrollment until the time of death (OS, overall survival). | From enrollment to death of patients. Estimated about 1 year. |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D056831 | Coordination Complexes |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |