Phase II Trial Evaluating Axitinib In Patients With Unresectable, Recurrent Or Metastatic Head And Neck Cancer
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).
Head and Neck Squamous Cell Carcinoma
Drug: Axitinib (AG-013736)
|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|
- 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.
- 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
|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)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01469546
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Francis P Worden, MD||University of Michigan Cancer Center|