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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Gastric Cancer
• Intervention / Treatment: Drug: Capecitabine, Cisplatin, Sorafenib

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

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

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Study Chair: Yoon-Koo Kang, MD, PhD, Asan Medical Center

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: November 28, 2007
• First Submitted That Met QC Criteria: November 28, 2007
• First Posted (Estimate): November 29, 2007

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 6, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: cisplatin; capecitabine; Gastric cancer; phase I; phase II; sorafenib
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Cisplatin; Sorafenib; Capecitabine
• Other Study ID Numbers: AMC0701