This study will be a prospective, single-institution, single-arm phase II study of Axitinib
in patients with unresectable recurrent and metastatic head and neck squamous cell carcinoma.
The subjects will be started on treatment with 5 mg of Axitinib twice a day continuously,
with subsequent dose escalation to 7 mg and then 10 mg twice a day in the absence of grade 2
or worse toxicities. This will be followed by clinical and/or radiologic response assessment
after 8 weeks and subsequently every 2 months until disease progression or intolerable
- Histologically documented squamous cell head and neck cancer with or without
metastases, not amenable to curative treatment; or the patient has documented refusal
of curative treatment.
- Presence of measurable disease per protocol.
- Adequate bone marrow, hepatic, and renal function.
- Age ≥18 years.
- ECOG (Eastern Cooperative Oncology Group scoring system used to quantify general
well-being and activities of daily life; scores range from 0 to 5 where 0 represents
perfect health and 5 represents death.) performance status of 0-2.
- Life expectancy of ≥12 weeks.
- No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood
pressure readings taken at least 30 minutes apart. Patients whose hypertension is
controlled by antihypertensive therapies are eligible.
- Women of childbearing potential must have a negative serum or urine pregnancy test
within 3 days prior to treatment.
- Signed and dated informed consent
- Willingness and ability to comply with scheduled visits, treatment plans, including
willingness to take Axitinib, laboratory tests, and other study procedures.
- If a curative treatment option in the form of chemoradiation exists in a patient with
unresectable disease, this has to be attempted first and must have failed, unless the
patient has documented refusal of curative treatment.
- Central lung lesions involving major blood vessels (arteries or veins) or a tumor
encasing major blood vessels (i.e. carotid artery).
- Active hemoptysis
- Gastrointestinal abnormalities causing impaired absorption requiring intravenous
alimentation, prior surgical procedures affecting absorption including gastric
resection, treatment for active peptic ulcer disease in the past 6 months, active
gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis,
hematochezia or melena in the past 3 months without evidence of resolution documented
by endoscopy or colonoscopy, malabsorption syndromes.
- Previous treatment with anti-angiogenesis agents including thalidomide, or inhibitors
of epidermal growth factor (EGF), platelet derived growth factor (PDGF), or fibroblast
growth factors (FGF) receptors within 30 days preceding study entrance.
- Current use or anticipated inability to avoid use of drugs that are known potent
- Current use or anticipated inability to avoid use of drugs that are known CYP3A4/5
- Active seizure disorder or evidence of untreated or progressive brain metastases,
spinal cord compression, or carcinomatous meningitis (Subjects with brain metastases
are eligible if they have been treated and there is no CT or MRI evidence for at least
4 weeks after CNS (Central Nervous System) metastasis treatment is complete.).
- A serious uncontrolled medical disorder or active infection that would impair their
ability to receive study treatment.
- History of a malignancy (other than head and neck cancer) except those treated with
curative intent for skin cancer (other than melanoma), in situ breast or in situ
cervical cancer, or those treated with curative intent for any other cancer with no
evidence of disease for 2 years.
- Major surgery <4 weeks or radiation therapy <2 weeks of starting the study treatment.
Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is
at least one measurable lesion that has not been irradiated.
- Dementia or significantly altered mental status that would prohibit the understanding
or rendering of informed consent and compliance with the requirements of this
- Patients (male and female) having procreative potential who are not willing or not
able to use adequate contraception or practicing abstinence
- Women who are pregnant or breast-feeding.
- Patients with history of bleeding diathesis, arterial thromboembolism, current use of
therapeutic anticoagulation with oral vitamin K antagonists, factor Xa inhibitors,
heparin products, oral direct thrombin inhibitors, or presence of non-healing wounds.
Low-dose anticoagulants for maintenance of patency of central venous access device or
prevention of deep venous thrombosis is allowed.
- Patients residing in prison.
- Prior experimental therapy within 30 days of planned start of this trial.
- HIV virus infection irrespective of viral load, treatment status, or CD4 count, or
acquired immunodeficiency syndrome (AIDS)-related illness. HIV testing is not required
by this protocol.
- Any of the following within the 12 months prior to study drug administration:
myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft,
symptomatic congestive heart failure, cerebrovascular accident or transient ischemic
- History of deep vein thrombosis or pulmonary embolism within 6 month of anticipated
starting of Axitinib.
- Availability of curative treatment option for the patient's cancer, whether surgery,
chemotherapy, radiation, or combination thereof, unless the patient has documented
refusal of curative treatment.
- Increased risk of wound dehiscence or presence of non-healing wounds.