| Eligibility |
Inclusion Criteria:
- Advanced metastatic, progressing carcinoid or pancreatic islet cell cancers
- No prior targeted treatment (tx) or anti-angiogenic therapy; patients may have
received one line of prior therapy with octreotide, locoregional therapy; continuation
of concurrent octreotide is allowed; patients will be maintained on octreotide
(sandostatin) for the duration of their treatment
- Life expectancy of at least 12 weeks (3 months)
- Subjects must be able to understand and be willing to sign the written informed
consent form (ICF); a signed ICF must be appropriately obtained prior to the conduct
of any trial-specific procedure
- All acute toxic effects of any prior treatment have resolved to National Cancer
Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v)4.0
grade 1 or less at the time of signing the informed consent form (ICF); exceptions to
this include alopecia
- Total bilirubin =< 1.5 x the upper limits of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5
x ULN for subjects with liver involvement of their cancer)
- Alkaline phosphastase limit =< 2.5 x ULN (=< 5 x ULN for subjects with liver
involvement of their cancer)
- Lipase =< 1.5 x the ULN
- Amylase =< 1.5 x the ULN
- Serum creatinine =< 1.5 x the ULN
- International normalized ratio (INR)/ partial thromboplastin time (PTT) < 1.5 x ULN;
(subjects who are treated with an agent such as warfarin or heparin will be allowed to
participate provided that no prior evidence of underlying abnormality in coagulation
parameters exists; close monitoring [day 5 of cycle 1 and day 1 of each cycle] is
mandatory) will be performed until INR/PTT is stable based on a measurement that is
pre-dose as defined by the local standard of care)
- Platelet count >= 100,000 /mm^3
- Hemoglobin (Hb) >= 9 g/dL
- Absolute neutrophil count (ANC) >= 1,500/mm^3; blood transfusion to meet the inclusion
criteria will not be allowed
- Glomerular filtration rate (GFR) >= 30 ml/min/1.73 m^2 according to the Modified Diet
in Renal Disease (MDRD) abbreviated formula
- Women of childbearing potential must have a negative serum pregnancy test performed
within 7 days prior to the start of study drug; post-menopausal women (defined as no
menses for at least 1 year) and surgically sterilized women are not required to
undergo a pregnancy test; the definition of adequate contraception will be based on
the judgement of the investigator
- Subjects (men and women) of childbearing potential must agree to use adequate
contraception beginning at the signing of the ICF until at least 3 months after the
last dose of study drug; the definition of adequate contraception will be based on the
judgment of the principal investigator or a designated associate
- Subject must be able to swallow and retain oral medication
- Southwest Oncology Group (SWOG) performance status 0-1
- Patients must have measurable disease
Exclusion Criteria:
- Previous assignment to treatment during this study; subjects permanently withdrawn
from study participation will not be allowed to re-enter study
- Uncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm
Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical management
- Active or clinically significant cardiac disease including:
- Congestive heart failure - New York Heart Association (NYHA) > class II
- Active coronary artery disease
- Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or
digoxin
- Unstable angina (anginal symptoms at rest), new-onset angina within 3 months
before randomization, or myocardial infarction within 6 months before
randomization
- Evidence or history of bleeding diathesis or coagulopathy
- Any hemorrhage or bleeding event >= NCI-CTCAE grade 3 within 4 weeks prior to start of
study medication
- Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular
accident (including transient ischemic attacks) deep vein thrombosis or pulmonary
embolism within 6 months of start of study treatment
- Subjects with any previously untreated or concurrent cancer that is distinct in
primary site or histology from carcinoid or pancreatic islet cancer except cervical
cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor; subjects
surviving a cancer that was curatively treated and without evidence of disease for
more than 3 years before randomization are allowed; all cancer treatments must be
completed at least 3 years prior to study entry (i.e., signature date of the informed
consent form)
- Patients with pheochromocytoma
- Known history of human immunodeficiency virus (HIV) infection or current chronic or
active hepatitis B or C infection requiring treatment with antiviral therapy
- Ongoing infection > grade 2 NCI-CTCAE v4.0
- Presence of a non-healing wound, non-healing ulcer, or bone fracture
- Renal failure requiring hemo-or peritoneal dialysis
- Dehydration grade >= 1 NCI-CTCAE v4.0
- Patients with seizure disorder requiring medication
- Persistent proteinuria >= grade 3 NCI-CTCAE v4.0 (> 3.5 g/24 hrs, measured by urine
protein:creatinine ratio on a random urine sample)
- Interstitial lung disease with ongoing signs and symptoms at the time of informed
consent
- Pleural effusion or ascites that causes respiratory compromise (>= NCI-CTCAE version
4.0 grade 2 dyspnea)
- History of organ allograft (including corneal transplant)
- Known or suspected allergy or hypersensitivity to any of the study drugs, study drug
classes, or excipients of the formulations given during the course of this trial
- Any malabsorption condition
- Women who are pregnant or breast-feeding
- Any condition which, in the investigator's opinion, makes the subject unsuitable for
trial participation
- Substance abuse, medical, psychological or social conditions that may interfere with
the subject's participation in the study or evaluation of the study results
- Patients with known brain metastases should be excluded from this clinical trial
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to regorafenib or other agents used in study
- Uncontrolled, intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
- Excluded therapies and medications, previous and concomitant
- Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery,
immunotherapy, biologic therapy, or tumor embolization) other than study
treatment (regorafenib)
- Prior use of regorafenib
- Concurrent use of chemotherapy, radiotherapy or another investigational drug or
device therapy (i.e., outside of study treatment) during, or within 4 weeks of
trial entry (signing of the ICF)
- Major surgical procedure, open biopsy, or significant traumatic injury within 28
days before start of study medication
- Use of any herbal remedy (e.g. St. John's wort [Hypericum perforatum])
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