Advanced Gastric Cancer
Conditions
Keywords
Gastric cancer, capecitabine, cisplatin, sorafenib, phase I, phase II
Brief summary
There is strong scientific rationale for exploring the role of sorafenib with capecitabine and cisplatin (XP) in AGC. XP is a new standard of care in AGC and sorafenib is a novel signal transduction inhibitor that prevents tumor cell proliferation and angiogenesis through blockade of the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGF-R2 and PDGFR-beta.
Interventions
DRUGCapecitabine, Cisplatin, Sorafenib
Capecitabine ( ) mg/m2 bid D1-D15 Cisplatin 80 mg/m2 D1 Sorafenib ( ) mg bid PO daily every 3 weeks
Sponsors
Asan Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Having given signed written informed consent * Unresectable advanced gastric adenocarcinoma, initially diagnosed or recurred * No history of chemotherapy or radiation * Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) * Age 18-75 years * Estimated life expectancy of more than 3 months * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Adequate bone marrow function (absolute neutrophil count \> 1,500/µL, platelets \> 100,000/µL, hemoglobin \> 8g/dl), * Adequate kidney function (creatinine clearance \> 60 ml/min) * Adequate liver function (bilirubin \< 2.0 mg/dL, transaminases levels \< 3 times the upper normal limit \[5 times for patients with liver metastasis\])
Exclusion criteria
* Past or concurrent history of neoplasm other than gastric adenocarcinoma, except for curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix uteri * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start * Presence of central nervous system metastasis * Obvious peritoneal seeding or bowel obstruction * Evidence of serious gastrointestinal bleeding * Peripheral neuropathy (National Cancer Institute Common Terminology Criteria for Adverse Event version 3.0 \> Grade I) * History of significant neurologic or psychiatric disorders * Pregnant or lactating women, women of childbearing potential not employing adequate contraception * Other serious illness or medical conditions * Known allergy to study drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) | 28weeks | Number of Participants who Experienced Dose Limiting Toxicities (DLTs) |
| Progression-free Survival | 1 year | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 6 months | Tumor response was assessed every two cycles by RECIST(v1.0) using the same imaging techniques and methods used at baseline. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR., or similar definition that is accurate and appropriate |
| Overall Survival | 28 months | — |
| Toxicity Profile (According to National Cancer Institute Common Terminology Criteria for Adverse Event Version 3.0) | 28weeks | Number of patients who experienced toxicity from study treatment to evaluate the safety and tolerability of Capecitabine and cisplatin plus sorafenib |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| XP Plus Sorafenib Capecitabine and cisplatin plus sorafenib | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | XP Plus Sorafenib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 53.7 years STANDARD_DEVIATION 11.8 |
| Region of Enrollment Korea, Republic of | 21 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 21 |
| serious Total, serious adverse events | 4 / 21 |
Outcome results
Primary
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
Number of Participants who Experienced Dose Limiting Toxicities (DLTs)
Time frame: 28weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XP Plus Sorafenib | Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) | 3 participants |
Primary
Progression-free Survival
Time frame: 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| XP Plus Sorafenib | Progression-free Survival | 10.0 Months |
Secondary
Overall Survival
Time frame: 28 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| XP Plus Sorafenib | Overall Survival | 14.7 Months |
Secondary
Response Rate
Tumor response was assessed every two cycles by RECIST(v1.0) using the same imaging techniques and methods used at baseline. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR., or similar definition that is accurate and appropriate
Time frame: 6 months
Population: Patients who had measurable lesions were included for the response rates
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XP Plus Sorafenib | Response Rate | 62.8 percentage of participants |
Secondary
Toxicity Profile (According to National Cancer Institute Common Terminology Criteria for Adverse Event Version 3.0)
Number of patients who experienced toxicity from study treatment to evaluate the safety and tolerability of Capecitabine and cisplatin plus sorafenib
Time frame: 28weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| XP Plus Sorafenib | Toxicity Profile (According to National Cancer Institute Common Terminology Criteria for Adverse Event Version 3.0) | 21 participants |