| Eligibility |
Inclusion Criteria:
- Signed informed consent before any study procedures completed.
- Subjects with historically confirmed advanced metastatic or refractory solid
malignancy who are not candidates for standard therapy.
- Male/female subjects = 18 years of age
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
- Women of childbearing potential must have a negative urine pregnancy test performed
within 7 days before starting study treatment. Women of childbearing potential and men
must agree to use adequate contraception since the signing of informed consent until
at least 8 weeks after the last study drug administration.
- Life expectancy of at least 8 weeks.
- Adequate bone marrow, and liver function as assessed by the designated laboratory
levels within 7 days of starting study treatment:
1. Platelet count = 100,000/cubic millimeters, hemoglobin (Hb) = 8.0 g/dl, absolute
neutrophil count (ANC) = 1500 cubic millimeters
2. total bilirubin = 1.5 times the upper limit of normal range (ULN). Mildly
elevated total bilirubin (<6 mg/dL) is allowed if Gilbert's syndrome is
documented
3. Alanine aminotransferase (ALT) and asparate aminotransferase (AST) = 2.5 times
ULN (= 5 times ULN for subjects whose cancer involves their liver including liver
metastasis).
4. Alkaline phosphatase limit = 2.5 times ULN (= 5 ULN for subjects whose cancer
involves their liver including liver metastasis)
5. Amylase and lipase = 1.5 times ULN
- International normalized ratio (INR) = 1.5 x ULN and partial thromboplastin time (PTT)
= 1.5 times ULN. Subjects who are being treated with heparin or warfarin are allowed
to participate.
- Estimated glomerular filtration rate (eGFR) = 60 mL/minute as calculated using the
Cockcroft-Gault formula
Exclusion Criteria:
- Prior treatment with regorafenib. Patients permanently withdrawn from the study will
not be allowed to re-enter the study
- Symptomatic metastatic brain or meningeal tumors unless the patient is greater than 6
months from definitive therapy, has no evidence of tumor growth on an imaging study
within four weeks prior to study entry and is not on dexamethasone and clinically
stable with respect to the tumor at the time of surgery.
- Major surgery, open biopsy or significant traumatic injury within 28 days before
starting the study treatment.
- History of organ allograft.
- Non-healing wound, skin ulcer or bone fracture.
- Uncontrolled intercurrent medical illness including uncontrolled hypertension defined
as systolic blood pressure > 150 millimeters of mercury (mmHg) or diastolic blood
pressure > 90 mmHg, despite medical management
- History of cardiac disease: congestive heart failure > New York Heart Association
(NYHA) Class II; unstable angina (symptoms of angina at rest), new-onset angina
(within the last 3 months), myocardial infarction within the past 6 months prior to
screening (Visit 1); cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
(expect for beta-blockers and digoxin).
- Pleural effusion or ascites with causes respiratory compromise (National Cancer
Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Grade = 2 dyspnea).
- Interstitial lung disease with ongoing signs and symptoms within 28 days before
starting the study treatment
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident
(including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
within 6 months before the start of study medication.
- Subjects with evidence or history of bleeding diathesis; any hemorrhage or bleeding
event CTCAE Grade = 3 or higher within 4 weeks of start of investigational treatment.
- Dehydration CTCAE Grade =1
- Unresolved toxicity higher than NCI-CTCAE version 4.0 Grade 1 (excluding alopecia,
anemia or lymphopenia) attributed to any prior systemic or radiation therapy or other
medical or surgical procedure
- Known hypersensitivity to regorafenib, study drug class, or excipients in the
formulation.
- Ongoing or active infection (bacterial, fungal or viral, e.g. human immunodeficiency
virus (HIV)) of NCI-CTCAE version 4.0 Grade = 2
- Seizure disorder requiring anti-convulsant therapy (such as steroids or
anti-epileptics)
- Pregnancy and lactation (breastfeeding)
- During the study, no other anticancer treatment, including any investigational new
drugs, is allowed. Anticancer therapy is defined as any agent or combination of agents
with clinically proven anticancer activity. Systemic anticancer therapy including
cytotoxic therapy, signal transduction inhibitors, immunotherapy and hormonal therapy
during this trial or within 28 days or 5 drug half lives (if drug half-life in subject
is known), whichever is shorter (or within 6 weeks or mitomycin C) before start of the
study treatment
- Use of hematopoietic growth factors, such as G-CSF (granulocyte colony-stimulating
factor), GM-CSF (granulocyte-macrophage colony-stimulating factor), erythropoietin,
and interleukin (IL-2, IL-3), within 3 weeks prior to first dose. Subjects taking
chronic erythropoietin consistent with institutional guidelines can be included.
- Close affiliation with the investigational site; e.g. a close relative of the
investigator or a dependent person (e.g. employee or student of the investigational
site)
- Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results.
- Inability to swallow oral medications.
|
