This research study is a Phase I clinical trial, which tests the safety of an investigational
drug and also tries to define the appropriate dose of the investigational drug to use for
further studies. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved Regorafenib for this
specific disease but it has been approved for other uses.
In this research study, the investigators are looking for the best dose of Regorafenib to
treat the participant's disease with. Researchers will also look at how effective the study
drug is in treating the participant's disease and if any side effects occur.
- Diagnosis of relapsed/refractory advanced malignancies. Specifically: relapsed
refractory refractory acute myeloid leukemia that have failed one line of prior
therapy, myelodysplastic syndrome that have failed hypomethylating agents,
myelofibrosis that have failed ruxolitinib or are ineligible for this therapy.
- 18 years of age or greater.
- ECOG performance status of 0-1.
- Able to provide informed consent.
- Subjects (men and women) of childbearing potential must agree to use adequate
contraception beginning at the signing of the ICF until at least 2 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.
- Able to swallow and retain oral medication.
- Normal organ and marrow function defined as:
- Total bilirubin ≤ 1.5 x the upper limits of normal (ULN) except for patients with
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
(≤ 5 x ULN for subjects with liver involvement of their cancer).
- Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver or bone
involvement of their cancer).
- Serum creatinine ≤ 1.5 x the ULN.
- International normalized ratio (INR)/ Partial thromboplastin time (PTT) ≤ 1.5 x
ULN. (Subjects who are prophylactically 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.)
- Previous assignment to treatment during this study. Subjects permanently withdrawn
from study participation will not be allowed to re-enter the study.
- Systemic antineoplastic therapy in the past 14 days (excluding hydroxyurea).
- Uncontrolled hypertension (systolic pressure >140 mmHg or diastolic pressure > 90 mmHg
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
- Unstable angina (anginal symptoms at rest), new-onset angina within 3 months
before randomization, or myocardial infarction within 6 months before
- Evidence or history of bleeding diathesis or coagulopathy.
- Eligible for, have a suitable donor and are willing to undergo Hematopoietic Stem Cell
- Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of
- Thrombotic, embolic, venous or arterial events, such as cerebrovascular accident
(including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
within 6 months of informed consent.
- Previously untreated or concurrent cancer that is distinct in primary site or
histology except cervical cancer in-situ, treated ductal carcinoma in situ of the
breast, curatively treated non-melanoma skin carcinoma, noninvasive aerodigestive
neoplasms or superficial bladder tumor. Subjects surviving a cancer that was
curatively treated and without evidence of disease for more than 3 years before
registration are allowed. All cancer treatments must be completed at least 3 years
prior to registration.
- Known history of human immunodeficiency virus (HIV) infection or current chronic or
active hepatitis B or C infection requiring treatment with antiviral therapy.
- Presence of a non-healing wound, non-healing ulcer or bone fracture.
- Major surgical procedure or significant traumatic injury within 28 days before start
of study medication.
- Renal failure requiring hemo-or peritoneal dialysis.
- 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
- 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, or intend to become pregnant during the
study. 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.
- Substance abuse, medical, psychological or social conditions that may interfere with
the subject's participation in the study or evaluation of the study results.
- Presence of unresolved toxicities from prior anticancer therapy, defined as having not
resolved to NCI CTCAE v4.03 grade 0 or 1 with the exception of alopecia. Subjects with
irreversible toxicity that is not reasonably expected to be exacerbated by regorafenib
(e.g. hearing loss, neuropathy) may be included after consultation with the principal
- Uncontrolled inter-current illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements