Cetuximab and Dasatinib in Recurrent Squamous Cell Carcinoma

Study Overview
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Brief Summary
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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.

Detailed Description
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Patients must have recurrent SCCHN and may have received any number of prior palliative systemic therapies for recurrent disease (without cetuximab or othr EGFR inhibitor). One prior curative regimen (induction, primary or postoperative chemoradiotherapy) should have been given AND all patients should have been exposed to cetuximab as part of prior potentially curative treatment.Those who have received a prior Src kinase inhibitor or EGFR inhibitor other than cetuximab are not eligible. Patients will be tested for serum IL-6. If IL-6 is detectable, the patient will be ineligible. If IL-6 is not detected, the patient will be eligible for the study. Subjects more than 2 weeks post last dose of Cetuximab will receive an initial loading dose 400 mg/m2 on cycle 1, day 1. Subjects who have received Cetuximab within 2 weeks of starting study will start Cycle 1 with dose of 250 mg/m2. Dasatinib will start 3 days after initial cetuximab study dose on cycle 1 (i.e cycle 1, day 4), and continue without interruption.

Official Title
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Phase II Trial of Cetuximab and Dasatinib in Patients With Cetuximab-resistant, Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck and Low Serum IL-6

Conditions
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Squamous Cell Carcinoma Of The Head And Neck

Intervention / Treatment
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* Drug: Cetuximab
* Drug: Dasatinib


Participation Criteria
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Eligibility Criteria
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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: absolute neutrophil count >1,200/µL platelets >100,000/µL total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal 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).

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: CETUXIMAB AND DASATINIB<br>Cetuximab on a standard weekly schedule (see Section 6.2). Group 1 (subjects more than 2 weeks post last dose of Cetuximab): Loading dose of 400 mg/m2 on cycle 1, day 1 then 250 mg/m2 IV weekly. Group 2 (subjects last Cetuximab treatment within 2 weeks): Cycle 1 will start at a dose of 250 mg/m2 Dasatinib 150 mg once daily without interruption. On the FIRST cycle (1 cycle is 3 weeks) dasatinib will start 3 days after the cetuximab loading dose (i.e. cycle 1, day 4) to avoid headache as shown on the previous phase I trial. Treatment will continue until progression. | Drug: Cetuximab<br>* Cetuximab 250 mg/m2 IV weekly after loading dose 400 mg/m2 on cycle 1, day 1<br>* Other names: Erbitux;Drug: Dasatinib<br>* Dasatinib 150 mg po<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Number of patients experiencing a Complete Response (CR) + Partial Response (PR) to study treatment / Total number of evaluable patients, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | Up to 36 months | 
| Response to Treatment | Response of evaluable patients to treatment, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) |  | Up to 36 months | 
| Overall Survival (OS) | From date of entry into the study until the date of death from any cause, assessed up to 60 months. | Up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cetuximab, Dasatinib, Squamous Cell, Head and Neck, After Cetuximab Containing Chemoradiotherapy, Recurrent, Metastatic