Phase II Trial Evaluating Axitinib In Patients With Unresectable, Recurrent Or Metastatic Head And Neck Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Michigan Cancer Center
Sponsor:
Information provided by (Responsible Party):
Francis (Frank) Worden, University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT01469546
First received: October 24, 2011
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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).


Condition Intervention Phase
Head and Neck Squamous Cell Carcinoma
Drug: Axitinib (AG-013736)
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial Evaluating Axitinib (AG-013736) In Patients With Unresectable, Recurrent Or Metastatic Head And Neck Cancer

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • Progression-free survival (PFS) rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the 6-months progression-free survival (PFS) rate in patients with unresectable recurrent and metastatic head and neck cancer treated with Axitinib.


Secondary Outcome Measures:
  • Objective Response Rate and Disease Control Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the objective response rate (complete and partial response), and the disease control rate (complete response+partial response+stable disease), in patients with unresectable recurrent and metastatic head and neck cancer treated with Axitinib.

  • Toxicities [ Time Frame: While on axitinib and for 28 days after cessation of axitinib ] [ Designated as safety issue: Yes ]
    % of patients who develop these while on treatment and for 28 days after cessation of axitinib, and graded in severity per CTCAE v. 3.0 and as described in the protocol

  • Progression-Free Survival Rate [ Time Frame: 2 and 4 month ] [ Designated as safety issue: No ]
    To evaluate 2- and 4-month PFS rates in patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN) treated with Axitinib.

  • Dynamic between VEGF, EGF, PDGF, HGF, FGF and their receptors, as well as IL-6, IL-8, Jak2 and STAT3 upon treatment with Axitinib [ Time Frame: prior to initiation of therapy, 2, 4 and 8 weeks ] [ Designated as safety issue: No ]
    Data about blood levels of VEGF, EGF, PDGF, HGF, FGF, IL-6, IL-8 will be obtained from blood samples at four time points (prior to initiation of therapy, 2, 4 and 8 weeks).

  • Correlation of above data, as well as patients' HPV (Human Papilloma Virus) status and tumor microvessel density [ Time Frame: prior to initiation of therapy and at 4 weeks ] [ Designated as safety issue: No ]
    Correlation of these data, as well as patients' HPV (Human Papilloma Virus) status determined by p16 immunocytochemical testing and PCR on pretreatment biopsy, and tumor microvessel density determined by immunocytochemical testing with anti-CD31 antibody on biopsy specimens prior to initiation of therapy and at 4 weeks, with clinical outcomes, such as degree and of response, progression-free and overall survival.

  • Linear mixed effects regression to compare the change in each marker over time between responders and non-responders [ Time Frame: 8 weeks to 6 months ] [ Designated as safety issue: No ]
    -- Linear mixed effects regression will be used to compare the change in each marker over time between responders (complete or partial response) and non-responders at 8 weeks, or between patients progressed versus not progressed at 6 months (excluding patients that have not been followed for at least 6 months)

  • Prognostic and/or predictive pattern [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    prognostic and/or predictive pattern of changes that would allow prospective selection of patients who are likely to benefit from axitinib therapy


Estimated Enrollment: 40
Study Start Date: January 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Axitinib (AG-013736)
A prospective, single-institution, single-arm phase II study of Axitinib in patients with unresectable recurrent and metastatic head and neck squamous cell carcinoma who have received no more than two prior lines of systemic therapy for recurrent or metastatic head and neck cancer.
Drug: Axitinib (AG-013736)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01469546

Locations
United States, Michigan
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Cancer Answer Line    800-865-1125      
Principal Investigator: Francis P Worden, MD         
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Francis P Worden, MD University of Michigan Cancer Center
  More Information

No publications provided

Responsible Party: Francis (Frank) Worden, Associate Professor of Internal Medicine, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT01469546     History of Changes
Other Study ID Numbers: UMCC 2011.053, HUM00051095
Study First Received: October 24, 2011
Last Updated: May 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan Cancer Center:
Squamous Cell Carcinoma of the Head and Neck

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Axitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014