| Eligibility |
Inclusion Criteria:
- The participant (or legally representative if applicable) provides written informed
consent for the trial.
- Patients with histologically confirmed glioblastoma or other grade IV malignant glioma
(i.e. gliosarcoma, small cell glioblastoma, etc.), recurrent after prior external-beam
fractionated radiotherapy and temozolomide chemotherapy.
- Patients with documented radiographic progression following bevacizumab therapy for
treatment of glioblastoma
- Patients with up to 3 prior recurrences are allowed (patients could have received
bevacizumab or bevacizumab containing regimen either in first or second recurrence).
- Karnofsky performance status = 70%.
- Patients must have the following laboratory values:
- Absolute neutrophil count (ANC) = 1.5 x 109/L
- Platelets = 100 x 109/L
- Hemoglobin (Hgb) > 9 g/dL
- Serum total bilirubin: = 1.5 x ULN
- ALT and AST = 3.0 x ULN
- Serum creatinine = 1.5 x ULN
- Blood coagulation parameters: INR = 1.5
- Minimum interval since completion of radiation treatment is 12 weeks
- Minimum interval since last drug therapy:
- 3 weeks since last non-cytotoxic therapy
- 3 weeks must have elapsed since the completion of a non-nitrosourea containing
chemotherapy regimen
- 6 weeks since the completion of a nitrosourea containing chemotherapy regimen.
- 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 judgment 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 least2 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.
- Patients must have no concurrent malignancy except curatively treated basal or
squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast,
adequately treated stage I or II cancer from which the patient is in complete
remission. Patients with other prior malignancies must be disease-free for = three
years.
- Patients must be maintained on a stable or decreasing corticosteroid regimen from the
time of their baseline scan until the start of treatment and/or for at least 5 days
before starting treatment. The maximum dosing of corticosteroid therapy is 4mg/day.
- Life expectancy of at least 12 weeks (3 months).
- Subject must be able to swallow and retain oral medication.
Exclusion Criteria:
- Patients who have had previous treatment with Regorafenib
- Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or
intra-pelvic), open biopsy or significant traumatic injury = 4 weeks prior to starting
study drug, or patients who have had minor procedures, percutaneous biopsies or
placement of vascular access device = 1 week prior to starting study drug, or who have
not recovered from side effects of such procedure or injury
- Patients with impaired cardiac function or clinically significant cardiac diseases,
including any of the following:
- Congestive heart failure - New York Heart Association (NYHA) > Class II
- History or presence of serious uncontrolled ventricular arrhythmias. Cardiac
arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
- Clinically significant resting bradycardia (defined as bradycardia that required
intervention)
- Active coronary artery disease defined as Any of the following within 6 months prior
to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary
Artery Bypass Graft (CABG)
- Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism
(PE) in the last 6 months
- Uncontrolled hypertension (defined by a SBP = 160 mm Hg or DBP = 100 mm Hg despite
anti-hypertensive medications)
- Patients with cirrhosis, or active viral or nonviral hepatitis.
- Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not
mandatory)
- Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.
active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable
safety risks or compromise compliance with the protocol
- Pregnant or breast-feeding women
- Patients with known hypersensitivity to Chinese hamster ovary cell products or other
recombinant human, chimeric, or humanized antibodies
- Patients with active bleeding or pathologic conditions that carry a high risk of
bleeding, (i.e. hereditary hemorrhagic telangiectasia).
- Patients who are currently receiving anticoagulation treatment (warfarin is not
allowed, low weight heparin is allowed). Evidence or history of bleeding diathesis or
coagulopathy.
- Patients unwilling or unable to comply with the protocol
- Any hemorrhage or bleeding event = NCI CTCAE v5.0 Grade 3 within 4 weeks prior to
start of study medication.
- Patients with phaeochromocytoma.
- Ongoing infection > Grade 2 NCI-CTCAE v5.0.
- Presence of a non-healing wound, non-healing ulcer, or bone fracture.
- Persistent proteinuria = Grade 3 NCI-CTCAE v5.0 (> 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
5.0 Grade 2 dyspnea).
- 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.
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, other agents being investigated in combination with regorafenib).
- Prior use of regorafenib.
- Concurrent use of another investigational drug or device therapy (i.e., outside of
study treatment) during, or within 4 weeks of trial entry (signing of the informed
consent form).
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
before start of study medication.
- Therapeutic anticoagulation with Vitamin-K antagonists (e.g., warfarin)
- Use of any herbal remedy (e.g. St. John's wort [Hypericum perforatum]).
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