Phase II Trial Evaluating Axitinib In Patients With Unresectable, Recurrent Or Metastatic Head And Neck Cancer
Condition: Head and Neck Squamous Cell Carcinoma
MeSH terms: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck
Intervention: Axitinib (AG-013736)
Intervention description: 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 (defined per RECIST [Response Evaluation Criteria In Solid Tumors] criteria, or obvious progression on clinical or laryngoscopic/endoscopic exam) or intolerable toxicity (defined as below). During treatment on this protocol, all patients will be evaluated for safety. Correlative biomarker analysis will also be conducted.
Intervention MeSH terms: Axitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Squamous Cell Carcinoma of the Head and Neck

Summary:

      The purpose of this study is to investigate a new agent Axitinib in the treatment of head and
      neck cancer.

      This is a new drug that is given as a pill twice a day to treat cancer. This is one of the
      new, "smart" drugs. It binds to a protein on the surface of the cancer cell called VEGFR, and
      this way it slows down the growth of cancer cells and kills them. Head and neck cancer cells
      are known to carry this protein on their surface. Research in animals and in patients with
      other kinds of cancer showed that Axitinib can be effective at killing cancer cells, or
      stopping their growth, by this mechanism. It is generally a safe drug that is given by mouth.
      The investigators do not know, however, whether Axitinib is effective in head and neck
      cancer. This research study is being conducted to learn if Axitinib works in head and neck
      cancer, and also to learn to predict who would benefit from it. Four blood draws will be done
      to check special blood tests while the subjects are treated with Axitinib. These will be
      drawn at the same time as your routine labs, and there will not be additional sticks needed.
      A biopsy of the tumor before and after 1 month of treatment may be obtained to test how the
      cancer cells are responding to treatment. By testing these blood and tissue samples, the
      researchers will look at special tests (protein molecules) to try to determine what kind of
      head and neck patients would best respond to this drug. This is an open-label study, meaning
      that all subjects are on the active drug and there is no placebo (sugar pill).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically documented squamous cell head and neck cancer with or without
             metastases, not amenable to curative treatment.

          2. Presence of measurable disease by CT scan.

          3. Adequate bone marrow, hepatic, and renal function (including absence of proteinuria,
             PT (Prothrombin Time) <1.5, WBC (White Blood Cell count)≥ 3x109 cells/ml, ANC
             (Absolute Neutrophil Count) ≥ 1.5x109 cell/ml, platelets ≥75,000 cells/mm3, hemoglobin
             ≥ 9.0 g/dL, concentrations of total serum bilirubin within 1.5 x upper limit of normal
             (ULN), AST (Aspartate Aminotransferase), ALT (Alanine Aminotransferase) within 2.5x
             institutional upper limits of normal unless there are liver metastases in which case
             AST and ALT within 5.0 x ULN, serum creatinin clearance ≥ 60 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), documented
             within 14 days prior to initiation of Axitinib treatment.

          4. Age ≥18 years.

          5. ECOG (Eastern Cooperative Oncology Group) performance status of 0-2.

          6. Life expectancy of ≥12 weeks.

          7. 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.

          8. Women of childbearing potential must have a negative serum or urine pregnancy test
             within 3 days prior to treatment.

          9. 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.

         10. Willingness and ability to comply with scheduled visits, treatment plans, including
             willingness to take Axitinib, laboratory tests, and other study procedures.

        Exclusion Criteria:

          1. Central lung lesions involving major blood vessels (arteries or veins) or a tumor
             encasing major blood vessels (i.e. carotid artery).

          2. History of hemoptysis.

          3. 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.

          4. 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.

          5. Current use or anticipated inability to avoid use of drugs that are known potent
             CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole,
             itraconazole, erythromycin, clarithromycin, telithromycin, ergot derivatives,
             indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir,
             fosamprenavir , and delavirdine).

          6. Current use or anticipated inability to avoid use of drugs that are known CYP3A4 or
             CYP1A2 inducers (ie, carbamazepine, felbamate, omeprazole, phenobarbital, phenytoin,
             amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort).

          7. Active seizure disorder or evidence of brain metastases, spinal cord compression, or
             carcinomatous meningitis.

          8. A serious uncontrolled medical disorder or active infection that would impair their
             ability to receive study treatment.

          9. 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.

         10. 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.

         11. Dementia or significantly altered mental status that would prohibit the understanding
             or rendering of informed consent and compliance with the requirements of this
             protocol.

         12. Patients (male and female) having procreative potential who are not willing or not
             able to use adequate contraception or practicing abstinence.

         13. Women who are pregnant or breast-feeding.

         14. History of prior treatment with more than 2 lines of therapy for metastatic head and
             neck cancer.

         15. Patients with history of bleeding diathesis, DVT (deep venous thrombosis) or 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.

         16. Patients residing in prison.

         17. Prior experimental therapy within 30 days of planned start of this trial.

         18. HIV virus infection irrespective of viral load, treatment status, or CD4 count, or
             acquired immunodeficiency syndrome (AIDS)-related illness.

         19. 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.

         20. History of deep vein thrombosis or pulmonary embolism within 6 month of anticipated
             starting of Axitinib.