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Axitinib in Treating Patients with Recurrent or Metastatic Head and Neck Cancer That Cannot Be Removed by Surgery

Trial Status: Closed to Accrual

This phase II trial studies the best dose of axitinib and how well it works in treating patients with head and neck cancer that has come back, spread from where it started to other places in the body, or cannot be removed by surgery. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Inclusion Criteria

  • 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 by computed tomography (CT) scan
  • Absence of proteinuria
  • Prothrombin time (PT) < 1.5
  • White blood cells (WBC) >= 3 x 10^9 cells/ml
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9 cell/ml
  • Platelets >= 75,000 cells/mm^3
  • Hemoglobin >= 9.0 g/dL
  • Concentrations of total serum bilirubin within 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransaminase (AST), alanine aminotransaminase (ALT) within 2.5 x institutional upper limits of normal unless there are liver metastases in which case AST and ALT within 5.0 x ULN
  • Serum creatinine clearance >= 30 ml/min
  • Urinary protein < 2+ by urine dipstick (if dipstick is >= 2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is < 2 g per 24 hours)
  • Eastern Cooperative Oncology Group (ECOG) 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; the baseline systolic blood pressure readings must be =< 140 mm Hg, and the baseline diastolic blood pressure readings must be =< 90 mm Hg; 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 document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment
  • 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

Exclusion Criteria

  • Central lung lesions involving major blood vessels (arteries or veins) or a tumor encasing major blood vessels (i.e. carotid artery)
  • History of hemoptysis (defined as > 1/2 tablespoon [tsp] of bright red blood per day)
  • 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 strong cytochrome P450 family 3 subfamily A member 4/5 (CYP3A4/5) inhibitors (atazanavir, boceprevir, conivaptan, clarithromycin, grapefruit or grapefruit juice, indinavir, itraconazole, ketoconazole, nelfinavir, nefazodone, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole)
  • Current use or anticipated inability to avoid use of drugs that are known strong CYP3A4/5 inducers (carbamazepine, dexamethasone, fosphenytoin, phenytoin, phenobarbital, rifabutin, rifampin, rifapentine, St. John’s wort)
  • 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 magnetic resonance imaging (MRI) evidence for at least 4 weeks after central nervous system (CNS) 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 * Radiotherapy is defined as whole brain radiation, external beam radiation therapy (EBRT), or stereotactic brain radiation (SBRT)
  • Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
  • 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
  • Human immunodeficiency virus (HIV) virus infection irrespective of viral load, treatment status, or cluster of differentiation 4 (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 attack
  • 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


Ann Arbor
University of Michigan Comprehensive Cancer Center
Contact: Francis Paul Worden
Phone: 734-647-8902


I. To determine the 6 month overall survival in patients with unresectable, recurrent, and metastatic head and neck cancer treated with axitinib.


I. To determine the overall survival of patients treated with axitinib.

II. To determine the progression free survival of patients treated with axitinib.

III. To determine the disease control rate at 16 weeks and response rate as defined by Choi criteria.

IV. To determine the duration of response (as defined by Choi criteria) of patients treated with axitinib.

V. To assess the toxicities associated with the treatment of axitinib of patients treated with axitinib.

OUTLINE: This is a dose-escalation study.

Patients receive axitinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days until disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 28 days and every 3 months thereafter.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Michigan Comprehensive Cancer Center

Principal Investigator
Francis Paul Worden

  • Primary ID UMCC 2016.040
  • Secondary IDs NCI-2016-01064
  • ID NCT02762513