Capecitabine and Cisplatin (XP)+Sorafenib in Advanced Gastric Cancer (AGC): Sorafenib+XP

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I-II Study of Sorafenib (Nexavar®) in Combination With Capecitabine and Cisplatin (XP) in Patients With Advanced Gastric Cancer

Conditions
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Advanced Gastric Cancer

Intervention / Treatment
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* Drug: Capecitabine, Cisplatin, Sorafenib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>XP+sorafenib | Drug: Capecitabine, Cisplatin, Sorafenib<br>* Capecitabine ( ) mg/m2 bid D1-D15 Cisplatin 80 mg/m2 D1 Sorafenib ( ) mg bid PO daily every 3 weeks<br>|
| Placebo Comparator: B<br>XP | Drug: Capecitabine, Cisplatin, Sorafenib<br>* Capecitabine ( ) mg/m2 bid D1-D15 Cisplatin 80 mg/m2 D1 Sorafenib ( ) mg bid PO daily every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) | Number of Participants who Experienced Dose Limiting Toxicities (DLTs) | 28weeks | 
| Progression-free Survival |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 6 months | 
| Overall Survival |  | 28 months | 
| 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 | 28weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric cancer, capecitabine, cisplatin, sorafenib, phase I, phase II