| Eligibility |
Inclusion Criteria:
1. Patient who is able to understand the nature of this study and accepts to enter the
study by signing written informed consent
2. Patients who are = 20 years of age
3. 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)
4. Patient has at least one measurable lesion according to Response Evaluation Criteria
in Solid Tumors (RECIST) version 1.1.
5. 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
6. 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
7. 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:
1. Patient who has participated in other investigational studies and received any
investigational therapy within 4 weeks prior to study dosing
2. 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.
3. 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)
4. Patient with known leptomeningeal or brain metastasis (including those who require
glucocorticoids or intrathecal chemotherapy) by radiologic/histological evidence, or
only bone metastasis
5. 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
6. History of organ or bone marrow transplant
7. 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
8. 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)
9. 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)
10. History of stroke or transient ischemic attack within 6 months of study entry
11. 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
12. Patients with poorly controlled ascites and/or requirement for therapeutic
paracentesis more frequently than once every 3 months
13. Patients with HIV, acute HBV, and HCV (except hepatitis carriers) infections
14. Patient with known or suspected hypersensitivity to any agent given in the course of
this trial
15. 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
16. 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
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