Advanced or Metastatic Gastric Cancer
Conditions
Brief summary
Apatinib is a tyrosin-inhibitor agent targeting at vascular endothelial growth factor receptor (VEGFR), and it's anti-angiogenesis effect has been viewed in preclinical tests. The investigators' phase I study has shown that the drug's toxicity is manageable and the maximum tolerable daily dose is 850 mg. The purpose of this study is to determine whether apatinib can improve progression free survival or overall survival compared with placebo in patients with metastatic gastric carcinoma who failed two lines of chemotherapy.
Interventions
DRUGapatinib
apatinib 850 mg qd p.o. until disease progression or intolerable toxicity or patients withdrawal of consent
DRUGplacebo
placebo qd p.o. until disease progression or intolerable toxicity or patients withdrawal of consent
Sponsors
Fudan University
The 81 Hospital of PLA
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* ≥ 18 and ≤ 70 years of age * Histological confirmed advanced or metastatic adenocarcinoma of the stomach * Have failed for at least 2 lines of chemotherapy * Life expectancy of at least 12 weeks. * Eastern Cooperative Oncology Group Performance Status of 0 or 1 within 1 week before randomization. * At least one measurable lesion beyond stomach (larger than 10 mm in diameter by spiral CT scan) * Duration from the last therapy is more than 6 weeks for nitroso or mitomycin * More than 4 weeks for operation or radiotherapy * More than 4 weeks for cytotoxic agents or growth inhibitors * Adequate hepatic, renal, heart, and hematologic functions (HB ≥ 90g/L,platelets \> 80 ×10 E+9/L, neutrophil \> 1.5 × 10 E+9/L, serum creatinine ≤ 1× upper limit of normal(ULN), bilirubin \< 1.25× ULN, and serum transaminase ≤ 2.5× ULN).
Exclusion criteria
* Pregnant or lactating women * History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg). * Any factors that influence the usage of oral administration; Evidence of Central Nerves System(CNS) metastasis * Intercurrence with one of the following: coronary artery disease, arrhythmia ,heart failure and proteinuria ≥ (+) * International Normalize Ratio (INR) \> 1.5 and activated partial thromboplastin time（APPT） \> 1.5 × ULN * Abuse of alcohol or drugs * Certain possibility of gastric or intestine hemorrhage * Less than 4 weeks from the last clinical trial * Prior VEGFR inhibitor treatment * Disability of serious uncontrolled intercurrence infection Objective evidence of previous or current pulmonary fibrosis history, interstitial pneumonia, Pneumoconiosis, radiation pneumonitis, drug-related pneumonia, Pulmonary function damaged seriously etc.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival(PFS) | 30 months | Progression free survival of All the Evaluable Participants.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of diameters of target lesions, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| Overall Survival(OS) | 30 months | Overall Survival of the Participants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events | 30 months | — |
| Disease Control Rate(DCR) | 30 months | Disease control is defined as the proportion of patients who had a best response rating of complete response, partial response, or stable disease, and lasted at least 4 weeks. |
| Objective Response Rate(ORR) | 30 months | Objective Response Rate is defined as the proportion of patients with complete response(CR) or partial response(PR) |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Apatinib apatinib: apatinib 850 mg qd p.o. until disease progression or intolerable toxicity or patients withdrawal of consent | 176 |
| Placebo placebo: placebo qd p.o. until disease progression or intolerable toxicity or patients withdrawal of consent | 91 |
| Total | 267 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 22 | 3 |
| Overall Study | Death | 9 | 13 |
| Overall Study | Lack of Efficacy | 2 | 2 |
| Overall Study | Lost to Follow-up | 4 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Apatinib | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 55.01 years STANDARD_DEVIATION 9.92 | 56.08 years STANDARD_DEVIATION 9.74 | 55.37 years STANDARD_DEVIATION 9.81 |
| Sex: Female, Male Female | 44 Participants | 22 Participants | 66 Participants |
| Sex: Female, Male Male | 132 Participants | 69 Participants | 201 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 173 / 176 | 82 / 91 |
| serious Total, serious adverse events | 6 / 176 | 6 / 91 |
Outcome results
Primary
Overall Survival(OS)
Overall Survival of the Participants
Time frame: 30 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Apatinib | Overall Survival(OS) | 6.5 month |
| Placebo | Overall Survival(OS) | 4.7 month |
Primary
Progression Free Survival(PFS)
Progression free survival of All the Evaluable Participants.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of diameters of target lesions, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: 30 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Apatinib | Progression Free Survival(PFS) | 2.6 month |
| Placebo | Progression Free Survival(PFS) | 1.8 month |
Secondary
Disease Control Rate(DCR)
Disease control is defined as the proportion of patients who had a best response rating of complete response, partial response, or stable disease, and lasted at least 4 weeks.
Time frame: 30 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apatinib | Disease Control Rate(DCR) | 42.05 percentage of participants |
| Placebo | Disease Control Rate(DCR) | 8.79 percentage of participants |
Secondary
Objective Response Rate(ORR)
Objective Response Rate is defined as the proportion of patients with complete response(CR) or partial response(PR)
Time frame: 30 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apatinib | Objective Response Rate(ORR) | 2.84 percentage of participants |
| Placebo | Objective Response Rate(ORR) | 0.00 percentage of participants |
Secondary
Percentage of Participants With Adverse Events
Time frame: 30 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apatinib | Percentage of Participants With Adverse Events | 98.30 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events | 90.11 percentage of participants |