Imatinib Mesylate (Gleevec) and Docetaxel in Patients With Head and Neck Squamous Cell Cancer
Condition: Head and Neck Cancer; Squamous Cell Cancer
MeSH terms: Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell
Intervention: Imatinib Mesylate; Docetaxel
Intervention description: 400 mg by mouth daily; 60 mg/m^2 by vein (IV) over 1 hour every 3 weeks
Intervention MeSH terms: Docetaxel; Imatinib Mesylate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Head and Neck Cancer; Squamous Cell Cancer; Imatinib Mesylate; Gleevec; Imatinib; STI571; Docetaxel; Taxotere

Summary:

      Primary Objective:

        -  To determine the efficacy of the combination of imatinib mesylate and docetaxel in
           recurrent or metastatic head and neck squamous cell cancer by serial measurements of
           tumor response (extent, frequency, duration).

      Secondary Objectives:

        -  To assess the safety and tolerability of imatinib mesylate and docetaxel in patients
           with recurrent or metastatic head and neck squamous cell cancer.

        -  To explore the biologic effects of imatinib mesylate and docetaxel on tumor tissue by
           immunohistochemical analysis of microvessel density and phosphorylation of
           Platelet-derived growth factor receptors (PDGF-R).

        -  To explore the effects of imatinib mesylate and docetaxel on surrogate markers in serum.

        -  To assess the rate of survival.
    

Eligibility criteria:

        Inclusion Criteria:

          1. A written, voluntary informed consent form must be completed prior to beginning any
             study procedure.

          2. Patients >/= 18 years of age.

          3. Histologically documented diagnosis of head and neck squamous cell cancer

          4. At least one measurable site of disease and can be assessed by Response Evaluation
             Criteria In Solid Tumors (RECIST).

          5. Performance status 0-2 (Eastern Cooperative Oncology Group, ECOG)

          6. Patients must have adequate hepatic, renal, and bone marrow function, defined as the
             following: (1) total bilirubin < 1.5 * Upper Limits of Normal (ULN); (2) aspartate
             aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) < 2.5 * ULN;
             (3) creatinine < 1.5 * ULN; (4) ANC > 1.5 * 10^9/L; (5) platelets > 100 * 10^9/L.

          7. Female patients of childbearing potential must have negative pregnancy test within 7
             days before initiation of study drug dosing. Postmenopausal women must be amenorrheic
             for at least 12 months to be considered of non-childbearing potential. Male and female
             patients of reproductive potential must agree to employ an effective barrier method of
             birth control (i.e. condoms, diaphragm) throughout the study and for up to 3 months
             following discontinuation of study drug.

          8. Patients who have not been treated for recurrent or metastatic head and neck squamous
             cell carcinomas (HNSCC) (i.e. Patients who have been treated with chemotherapy for
             induction/adjuvant or concurrent therapy with radiation in the setting of definitive
             treatment but have now developed recurrent or metastatic disease are eligible).

        Exclusion Criteria:

          1. Prior exposure to docetaxel or imatinib mesylate.

          2. Patient has received any other investigational agents within 30 days of first day of
             study drug dosing.

          3. Patients with myocardial infarction within the past 6 months or New York Heart
             Association class 3 or 4 congestive heart failure.

          4. Female patients who are pregnant or breast-feeding.

          5. Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes,
             chronic renal disease, or active uncontrolled infection (i.e. septic).

          6. Patient has unstable brain metastasis. Unstable brain metastasis is defined as
             patients on steroid medication to control symptoms or patient with motor neurologic
             compromise due to brain metastasis. Patients with treated brain metastasis are
             eligible if they are > 6 weeks out from therapy and off all steroid medication.

          7. Patient has known chronic liver disease (i.e., chronic active hepatitis or cirrhosis).

          8. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection. HIV
             patients are at much greater risk of infection when receiving highly myelosuppressive
             agents (docetaxel and imatinib) and for safety reasons are not eligible for this
             trial.

          9. Patient received chemotherapy within 4 weeks (6 weeks for nitrosourea or mitomycin-C)
             prior to study entry, unless the disease is rapidly progressing.

         10. Patient previously received radiotherapy to >/= 25 % of the bone marrow

         11. Patient had a major surgery within 2 weeks prior to study entry.

         12. Patient with any significant history of non-compliance to medical regimens or with
             inability to grant reliable informed consent.

         13. Patients must agree not to use herbal remedies or other over-the-counter biologics
             (i.e. shark cartilage)

         14. History of hypersensitivity to docetaxel or other taxane therapy.

         15. History of severe hypersensitivity reaction to drugs formulated with polysorbate 80.

         16. Patients taking therapeutic levels of warfarin. However, patients receiving 1 mg daily
             for catheter related anticoagulation are eligible for the study.

         17. Prior pericardial effusion requiring intervention such as pericardiocentesis or
             pericardial window within 2 months of study entry.

         18. Patient is < 5 years free of another primary malignancy except: if the other primary
             malignancy is not currently clinically significant nor requiring active intervention,
             or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in
             situ. Existence of any other malignant disease is not allowed.

         19. Patients with a history of Regional Ileitis, Colitis, or Crohn's disease, or any other
             relevant medical history related to the integrity of the bowel wall as there may be an
             increased risk of bowel perforation with the combination of Docetaxel and Imatinib.