Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Patient who is able to understand the nature of this study and accepts to enter the study by signing written informed consent
Patients who are ≥ 20 years of age
Patients with histologically confirmed advanced or metastatic disease that is either refractory to or intolerant of existing standard therapy or for which no effective standard therapy that confers clinical benefit is available (patients may have received prior therapy with sorafenib if not intolerable)
Patient has at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Patient able to provide either an archived tumor sample or with accessible tumor for biopsy and willingness to provide it prior to initiation of study treatment
At least 4 weeks post any therapeutic modalities (e.g., surgery, radiotherapy, and therapeutic agents) prior to initial dosing except the palliative radiotherapy performed on non-study-related local lesions
Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2 8.Patient's life expectancy of at least 3 months

9.Patient has adequate hematopoietic, hepatic function and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:

Hemoglobin ≥ 9.0 g/dL
Absolute neutrophil count (ANC) ≥ 1,500 cells/μL
Total white blood cell (WBC) ≥ 3,000 cells/μL
Platelet ≥ 100,000 counts/μL
Total bilirubin ≤ 1.5× upper limit of normal (ULN) and no sign of jaundice
ALT and AST ≤ 2.5× ULN (≤ 5× ULN for patients with liver involvement)
ALP ≤ 5× ULN
Creatinine ≤ 1.5× ULN

Potassium, total calcium and magnesium within normal limits or correctable with supplements 10.Patient is able to take food and drug orally. 11.Patient is able to correctly operate the provided digital sphygmomanometer. 12.Female patient with childbearing potential should be confirmed of not being pregnant or not lactating at the screening and during the study.

13.Patient is willing to comply with protocol-stated requirements, instructions and restrictions.

Exclusion Criteria:

Patient who has participated in other investigational studies and received any investigational therapy within 4 weeks prior to study dosing
Patient carries history of primary malignancy other than the entry diagnosis except curatively treated non-melanoma skin cancer, cervical carcinoma in situ, or superficial bladder tumors within 5 years prior to study entry.
Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of GW5074 and sorafenib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
Patient with known leptomeningeal or brain metastasis (including those who require glucocorticoids or intrathecal chemotherapy) by radiologic/histological evidence, or only bone metastasis
Patient with history of significant cardiac disease including superior vena cava, unstable angina, congestive heart failure > class 2 per New York Heart Association (NYHA) classification, cardiac arrhythmias, cardiac ischemia/infarction, long QT-syndrome (i.e., QTc > 450 msec for males and > 470 msec for females), poorly controlled hypertension (systolic blood pressure > 150 mm-Hg and/or diastolic blood pressure > 90 mm-Hg on anti-hypersensitive medications), and valvular heart disease
History of organ or bone marrow transplant
Patient who has not recovered from side/toxic effects of previous therapy (i.e., NCI-CTCAE grade 1 or less) prior to the first dose of study medications
Patients who are receiving or with conditions requiring substances that are potent inducers of CYP3A4 activity (e.g., rifampin, St. John's wort, phenytoin, carbamazepine, phenobarbital, and dexamethasone)
Patients who are receiving or with conditions requiring sensitive substrates of CYP1A2, 1B1, 2C8, 2C19 and 3A4 with narrow therapeutic windows (e.g., theophylline, duloxetine, alosetron, tizanidine, repaglinide, omeprazole, S-mephenytoin, alfentanil, sirolimus, pimozide, and tacrolimus)
History of stroke or transient ischemic attack within 6 months of study entry
Patient with any hemorrhage/bleeding event (e.g., non-healing wound, ulcer, and bone fracture) ≥ NCI-CTCAE grade 2 within 28 days prior to study treatment, or history of bleeding diathesis or coagulopathy
Patients with poorly controlled ascites and/or requirement for therapeutic paracentesis more frequently than once every 3 months
Patients with HIV, acute HBV, and HCV (except hepatitis carriers) infections
Patient with known or suspected hypersensitivity to any agent given in the course of this trial
Patient with underlying medical, mental or psychological conditions that would impair the treatment compliance, or in the opinion of the investigator would not permit to participate in the study
Male and female patients (with child-bearing potential [between puberty and 2 years after menopause]) who are unwilling to practice an effective method of birth control (safe hormonal methods or/and barrier contraception) during the entire study period and 2 months after the last study drug intake