Cetuximab and Dasatinib in Treating Patients With Recurrent Squamous Cell Head and Neck Cancer Previously Treated With Cetuximab and Chemoradiation Therapy

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, TreatmentActive18 and over08-034
NCI-2011-03734, CA180264, NCT01488318

Trial Description

Summary

The purposes of this study are to determine if the combination of two drugs, cetuximab and dasatinib, is safe, at what dose levels they should be administered, and also to determine how the combination of the two drugs affects solid tumors.

Further Study Information

PRIMARY OBJECTIVES:

I. To study efficacy of dasatinib plus cetuximab, as measured by overall response rate (ORR) in order to determine whether or not dasatinib plus cetuximab is recommended for further study in squamous cell carcinoma of the head and neck (SCCHN).

SECONDARY OBJECTIVES:

I. To estimate time to progression and overall survival.

II. To evaluate the safety of the combination of dasatinib (D) and cetuximab (C) in this patient population.

III. To explore the mechanism of action epidermal growth factor receptor (EGFR) and SRC co-targeting.

IV. To explore the mechanism(s) of restoring EGFR sensitivity.

OUTLINE:

Patients receive cetuximab intravenously (IV) over 60-120 minutes on days 1, 8, and 15 and dasatinib orally (PO) once daily (QD) on days 1-21 (days 4-21 of course 1). Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Eligibility Criteria

Inclusion Criteria:

Patients must have recurrent SCCHN that has been previously treated with cetuximab as part of potentially curative therapy (i.e. with induction therapy, radiotherapy or chemoradiotherapy); the interval from completion of cetuximab and study treatment should be > 3 months

Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

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 (i.e. with radiotherapy or induction therapy); the last cetuximab dose should be > 3 months

Unlimited prior treatment with radiation or chemoradiotherapy

Any number of prior regimens for recurrent or metastatic SCCHN (i.e. palliative treatment) but without cetuximab or another EGFR inhibitor

Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

Life expectancy of greater than 12 weeks

Absolute neutrophil count >= 1,200/µL

Platelets >= 100,000/µL

Total bilirubin within normal institutional limits

Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase [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 cytochrome P450 3A4 (CYP3A4) inducers or potent inhibitors (+++) and should try to avoid taking proton pump inhibitors and histamine (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 Criteria:

Prior treatment with an EGFR inhibitor other than cetuximab at any time

Prior treatment with an EGFR inhibitor as part of a regimen for recurrent or metastatic SCCHN

Prior treatment with Src family kinase (SFK) inhibitor at any time

Patients who have not recovered from adverse events due to prior agents; a minimum interval of 3 weeks should have elapsed from prior radiotherapy and/or chemotherapy

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)

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

University of Pittsburgh Cancer Institute (UPCI)

  • National Cancer Institute
Michael Kevin Gibson, Principal Investigator

Trial Sites

U.S.A.

Pennsylvania
Pittsburgh

University of Pittsburgh Cancer Institute (UPCI)

Michael Kevin Gibson
Ph: 412-623-2393
Email: gibsonmk@upmc.edu

Michael Kevin Gibson
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01488318

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.