Cetuximab and Dasatinib in Recurrent Squamous Cell Carcinoma
Condition: Squamous Cell Carcinoma Of The Head And Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: Cetuximab; Dasatinib
Intervention description: Cetuximab 250 mg/m2 IV weekly after loading dose 400 mg/m2 on cycle 1, day 1; Dasatinib 150 mg po
Intervention MeSH terms: Cetuximab; Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cetuximab; Dasatinib; Squamous Cell; Head and Neck; After Cetuximab Containing Chemoradiotherapy; Recurrent; Metastatic

Summary:

      This is a single-arm, non-masked, open-label, Phase II study of cetuximab + dasatinib in
      recurrent Squamous Cell Carcinoma of The Head and Neck (SCCHN) that has recurred after
      cetuximab-containing therapy (please see attached schema).

      The primary endpoint 12-week PFS.
    

Eligibility criteria:

        Inclusion:

          -  Patients must have metastatic and/or recurrent SCCHN that has been previously treated
             with cetuximab.

          -  Undetectable baseline serum IL-6 NOTE : This eligibility criterion applies only to
             patients enrolling to the second, biomarker-enrichment stage of the trial.

          -  Measurable disease per RECIST 1.1.

          -  Unlimited prior treatment with radiation or chemoradiotherapy

          -  Any number of prior regimens for recurrent or metastatic SCCHN (i.e. palliative
             treatment) including cetuximab or other EGFR inhibitor

          -  Age >18 years

          -  ECOG performance status <2 (Karnofsky >60%, see Appendix A).

          -  Life expectancy of greater than 12 weeks.

          -  Patients must have normal organ and marrow function as defined below:

               1. absolute neutrophil count >1,200/µL

               2. platelets >100,000/µL

               3. total bilirubin within normal institutional limits

               4. AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal

               5. Creatinine up to 1.5 X normal institutional limits

          -  Ability to understand and the willingness to sign a written informed Consent document.

          -  Patients should not be taking concomitant medication that are CYP3A4 inducers or
             potent inhibitors and should try to avoid taking proton pump inhibitors and H2
             antagonists during rest of treatment period. The above medications will be continued
             only if medically necessary and their use will be noted.

          -  Sexually active women of childbearing potential must use an effective method of birth
             control during the course of the study, in a manner such that risk of failure is
             minimized. Prior to study enrollment, women of childbearing potential (WOCBP) must be
             advised of the importance of avoiding pregnancy during trial participation and the
             potential risk factors for an unintentional pregnancy. In addition, men enrolled on
             this study should understand the risks to any sexual partner of childbearing potential
             and should practice an effective method of birth control. All WOCBP MUST have a
             negative pregnancy test prior to first receiving investigational product. If the
             pregnancy test is positive, the patient must not receive investigational product and
             must not be enrolled in the study. In addition, all WOCBP should be instructed to
             contact the Investigator immediately if they suspect they might be pregnant (e.g.,
             missed or late menstrual period) at any time during study participation.

        Exclusion:

          -  Patients who have not recovered from adverse events due to prior agents. A minimum
             interval of 3 weeks should have elapsed from prior chemotherapy other than cetuximab.
             A minimum of 12 weeks should have elapsed from prior definitive radiotherapy, and a
             minimum of 1 week should have elapsed from prior palliative radiotherapy.

          -  Patients may not have received an investigational agent within 4 weeks of starting
             this trial.

          -  Patients with untreated brain metastases should be excluded from this clinical trial.

          -  History of allergic reactions to monoclonal antibodies.

          -  Inability to swallow oral medications (unless patients use a feeding tube in which
             case they are eligible).

          -  Uncontrolled angina or uncontrolled hypertension or any history of clinically
             significant ventricular arrhythmias (such as ventricular tachycardia, ventricular
             fibrillation, or Torsades de pointes).

          -  Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec) on the Bazett's
             correction.

          -  Diagnosed or suspected congenital long QT syndrome.

          -  Patients currently taking drugs that are generally accepted to have a risk of causing
             Torsades de Pointes including: quinidine, procainamide, disopyramide, amiodarone,
             sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine,
             haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol,
             methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine,
             sparfloxacin, lidoflazine.

          -  Any other uncontrolled intercurrent illness including, but not limited to, ongoing or
             active infection, symptomatic congestive heart failure, or psychiatric illness/social
             situations that would limit compliance with study requirements.

          -  History of significant bleeding disorder unrelated to cancer, including: diagnosed
             congenital bleeding disorders (e.g., von Willebrand's disease), diagnosed acquired
             bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).