| Eligibility |
Inclusion Criteria:
- Patients must have pathologically or cytologically confirmed adenoid cystic carcinoma.
Cancers arising from non-salivary gland primary sites are allowed.
- Patients must have recurrent and/or metastatic disease not amenable to potentially
curative surgery or radiotherapy.
- At least 2 weeks must have elapsed since the end of prior systemic treatment (4 weeks
for bevacizumab- containing regimens) or radiotherapy with resolution of all
treatment-related toxicity to NCI CTCAE Version 4.0 grade =1 (or tolerable grade 2) or
back to baseline (except for alopecia, lymphopenia, or hypothyroidism). Any number of
prior therapies for recurrent/metastatic ACC are allowed.
- Patients must have RECIST v1.1 measurable disease, defined as at least one lesion that
can be accurately measured in at least one dimension (longest diameter to be recorded
for nonnodal lesions and short axis for nodal lesions) as = 20 mm with conventional
techniques or as = 10 mm with spiral CT scan.
- Patients must have documentation of a new or progressive lesion on a radiologic
imaging study performed within 6 months prior to study enrollment (progression of
disease over any interval is allowed) and/or new/worsening disease related symptoms
within 6 months prior to study enrollment. Note: This assessment will be performed by
the treating investigator. Evidence of progression by RECIST criteria is not required.
- Patients must have archival tissue from the primary tumor or metastases available for
correlative studies. Either a paraffin block or twenty unstained slides are
acceptable. If twenty slides are not available, a lesser amount may be acceptable
after discussion with the Principal Investigator, Dr. Alan L. Ho.
- Patients must agree to undergo biopsy of a malignant lesion. Biopsies do not need to
be done if either the investigator or person performing the biopsy judges that no
tumor is accessible for biopsy or that biopsy poses too great of a risk to the
patient. Patients may also be exempt if frozen tumor tissue has been collected within
12 months of study enrollment that the Principal Investigator deems is
appropriate/sufficient for analysis on this protocol.
- Age = 18 years.
- ECOG performance status = 2 (Karnofsky = 60%,).
- Life expectancy of at least 12 weeks (3 months) as determined by the investigator.
- Life expectancy of at least 12 weeks (3 months) as determined by the investigator.
- Subjects must be able to understand and be willing to sign the written informed
consent form. A signed informed consent form must be appropriately obtained prior to
the conduct of any trial-specific procedure.
- Adequate bone marrow, liver and renal function as assessed by the following laboratory
requirements:
- Total bilirubin = 1.5 x the upper limits of normal (ULN) Alanine aminotransferase
(ALT) and aspartate amino-transferase (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
involvement of their cancer)
- Lipase = 1.5 x the ULN
- Amylase = 1.5 x the ULN Serum creatinine = 1.5 x the ULN or calculated creatinine
clearance >60 ml/min
- Platelet count = 100,000 /mm3, hemoglobin (Hb) = 9 g/dL, absolute neutrophil
count (ANC) = 1500/mm3. Blood transfusion to meet the inclusion criteria will not
be allowed.
- Women of childbearing potential must have a negative serum pregnancy test performed
within 2 weeks 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.
- Subjects (men and women) of childbearing potential must agree to use adequate
contraception beginning at the signing of the consent form 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.
Exclusion Criteria:
- Concurrent anti-cancer therapy (chemotherapy, definitive radiation therapy, surgery,
immunotherapy, biologic therapy, or tumor embolization) other than study treatment.
Concurrent therapy with bisphosphonates or denosumab for bone metastases is allowed.
Palliative radiation to non-target lesions is also allowed.
- Prior use of regorafenib.
- Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm
Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical management.
- 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).
- Concurrent use of strong CYP3A4 inhibitors (e.g. clarithromycin, grapefruit juice,
itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, and
voriconazole). or strong CYP3A4 inducers (e.g. rifampin, phenytoin, carbamazepine,
phenobarbital, and St. John's Wort).
- Use of any herbal remedy (e.g. St. John's wort [Hypericum perforatum])
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
before start of study medication.
- Active or clinically significant cardiac disease including:
Congestive heart failure - New York Heart Association (NYHA) > Class II.
- Active coronary artery disease that is not medically treated.
- 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.
- Therapeutic anticoagulation with Vitamin-K antagonists (e.g., warfarin) is not
allowed if the medication dose and/or INR/PTT are not considered stable by the
treating physician. If the dose and/or INR/PTT are stable, therapeutic
anticoagulation with Vitamin-K antagonists is allowed with close monitoring.
Anticoagulation with heparin or heparinoids is allowed.
- 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 a past or current diagnosis of another malignancy that will
interfere with conduct of the trial. Patients with past or current cancer
diagnoses other than ACC are allowed to enroll if the investigator believes it
will not interfere with trial conduct.
- Patients with phaeochromocytoma.
- Known history of human immunodeficiency virus (HIV) infection or current chronic
or active hepatitis B or C infection requiring treatment with antiviral therapy.
- Active infection that would impair the ability of the patient to receive study
treatment.
- Symptomatic metastatic brain or leptomeningeal tumors (asymptomatic or treated
metastatic brain and leptomeningeal tumors are allowed).
- Presence of a non-healing wound or non-healing ulcer that is not tumor related.
- Renal failure requiring hemo-or peritoneal dialysis.
- Patients with seizure disorder requiring medication.
- Interstitial lung disease with ongoing signs and symptoms at the time of informed
consent.
- 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.
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