Expansion Trial for Axitinib In Head And Neck Cancer

Study Overview
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Brief Summary
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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 toxicity.

Official Title
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Phase II Expansion Trial Evaluating Axitinib in Patients With Unresectable Recurrent, or Metastatic Head and Neck Cancer Utilizing Choi Response Criteria Phase

Conditions
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Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
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* Drug: Axitinib


Participation Criteria
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Eligibility Criteria
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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 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. Exclusion Criteria: 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 CYP3A4/5 inhibitors Current use or anticipated inability to avoid use of drugs that are known CYP3A4/5 inducers 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 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. 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Axitinib<br>Participants will receive 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 | Drug: Axitinib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Evaluable Patients Alive at 6 Months | Evaluable defined as any participant who receives at least one cycle of Axitinib. Number of evaluable patients and percentage of patients alive at 6 months is reported. | 6 Months after treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Overall Survival Time | median will be calculated by Kaplan-Meier method. | Up to approximately 2.5 years | 
| Median Progression Free Survival (PFS) Time | Median will be calculated by Kaplan-Meier method. | Up to approximately 2.5 years | 
| Best Overall Response | Tabulation of best response measured by Choi. Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progression (PD) at 16 weeks. CR is defined as no new lesions and the disappearance of all lesions. PR is defined as a decrease in size of ≥ 10% or a decrease in tumor density (HU) ≥ 15% on CT (Computerized Tomography), no new lesions and no obvious progression of non-measurable disease | 16 Weeks | 
| The Number of Patients That Experience Grade 3 or Worse Toxicities | Assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. For any treatment-related toxicity that occurred at any grade with a frequency greater than 10% in the overall study population, grade 3 or worse toxicities are shown here. | Duration of treatment and up to 28 days after treatment discontinuation |