Patient case: 60-year-old female with gastric cancer; genetic feature: EGFR

Clinical trial: A Study of Pazopanib With CAPEOX in AGC Patients

Summary: In order to improve survival of metastatic gastric cancer patients, we plan to to conduct a phase II trial of CapeOx with 800 mg once-daily pazopanib as a first-line chemotherapy in metastatic gastric cancer patients.

Detailed description: Despite improvements in the early diagnosis of gastric cancer, many patients present with inoperable disease and an effective, novel combination treatment is urgently needed for these patients population. A recent meta-analysis demonstrated that chemotherapy improves survival for patients with advanced gastric cancer compared with best supportive care alone [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.28-0.52] and that combination chemotherapy is superior to monotherapy (HR 0.83, 95% CI 0.74-0.93) (Wagner et al., 2006). For advanced gastric cancer, 5-FU in combination with cisplatin (FP regimen) is commonly used reference regimen, which are successfully replaced by capecitabine and oxaliplatin in recent phase III trial (Cunningham et al., 2008; Okines et al., 2009). In phase II trial, CAPEOX (capecitabine combined with oxaliplatin) regimen also showed promising activity for the metastatic gastric cancer (Park et al., 2006; Park et al., 2008). In order to improve survival of metastatic gastric cancer patients, various clinical trials incorporated novel molecularly targeted agent in combination with the reference arm.

Eligibility: Inclusion Criteria:
  -  Subjects who provide written informed consent
  -  Age over 18 years
  -  Histologically proven unresectable gastric cancer
  -  ECOG performance status of 0-2
  -  At least one uni-dimensionally measurable lesion by RECIST criteria ver 1.1
  -  Adequate organ system function absolute neutrophil count > 1,500/µL, platelets > 100,000/µL, hemoglobin > 9g/dl Total bilirubin < 1.5 times upper limit of normal (ULN), AST and ALT < 2.5 times ULN, PT (INR), PTT < 1.2 times UNL Serum creatinine less than 1.5 mg/dL or Calculated Ccr at least 50 mL/min, Urine Protein to Creatinine Ratio (UPC) less than 1
  -  female with Non-childbearing potential
  Exclusion Criteria:
  -  Prior malignancy
  -  History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug
  -  Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including
  -  Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
  -  Presence of uncontrolled infection
  -  Corrected QT interval (QTc) above 480 msecs using Bazett's formula
  -  History of any one or more of the following cardiovascular conditions within the past 6 months: Cardiac angioplasty or stenting, Myocardial infarction, Unstable angina, Coronary artery bypass graft surgery, Symptomatic peripheral vascular disease, Class II or higher congestive heart failure
  -  Poorly controlled hypertension while on antihypertensive agents
  -  History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
  -  Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer
  -  Evidence of active bleeding or bleeding diathesis
  -  Hemoptysis within 6 weeks of first dose of study drug
  -  Any serious and/or unstable preexisting medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
  -  Unable or unwilling to discontinue use of prohibited medications listed in the protocol
  -  Treatment with any of the following anti-cancer therapies;Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib; biologic therapy, immunotherapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib; No prior chemotherapy except adjuvant chemotherapy (Patients who received adjuvant chemotherapy at least 6 months prior to study entry will be allowed regardless of chemotherapeutic regimen
  -  Pre-existing grade 2 (or higher) motor or sensory neuropathy by CTCAE v4.0
  -  Known allergy to study drugs

Relevance to patient case: not relevant