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A Phase I/II Study of Dasatinib, Cetuximab and Radiation With or Without Cisplatin in Locally Advanced Squamous Cell Carcinoma of Head and Neck (HNSCC)

Phase 1/Phase 2
18 Years
Open (Enrolling)
Head and Neck Cancer

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Trial Information

A Phase I/II Study of Dasatinib, Cetuximab and Radiation With or Without Cisplatin in Locally Advanced Squamous Cell Carcinoma of Head and Neck (HNSCC)

Primary Objective for Phase I

1. To determine the maximally tolerated dose (MTD) of daily Oral dasatinib in combination
with cetuximab/RT in Cohort A, in patients with AJCC stage II (T2N0) and III (T1-2N1)
SCCHN of oral cavity, oropharynx, T2N0 hypopharynx, T2N0-1 supraglottic larynx.

2. To determine the MTD of daily oral dasatinib in combination with cisplatin/cetuximab/RT
in Cohort B, in patients with AJCC stage III (T3N0-1) and IV (T1-4N2-3M0, T4N0-1M0)
squamous cell carcinoma of oral cavity, oropharynx, hypopharynx, and larynx.

Primary Objectives of Phase II

1. To estimate the objective tumor response rate and toxicity in Patients treated in
expanded Cohort A and B.

Secondary Objectives of Phase II

1. To estimate the 2 year disease free survival of patients treated in Cohorts A and B.

2. To estimate the median overall survival in patients treated in Cohorts A and B.

3. To perform an exploratory analysis of biomarker expression on serial samples of tumor
and blood and to correlate biomarker expression with response and survival outcomes in
patients treated in Cohorts A and B.

4. To estimate the role of 18F-FDG PET as an early indicator of response in patients
treated in Cohorts A and B and correlate with clinical and pathological response and
survival outcomes.

Inclusion Criteria:

1. Patients must have a histologically confirmed operable or inoperable squamous cell
carcinoma of OC, OP, HP, or larynx prior to proceeding with treatment.

2. Patients must be AJCC stage II (T2N0) or III (T1-2N1) of oral cavity, oropharynx,
only T2N0 of hypopharynx, T2N0-1 supraglottic laryngeal cancers (AJCC Fifth Edition,
1997) for Arm A of the study, and must be AJCC stage III (T3N0-1) or IV (T1-4N2-3M0,

3. Patients must have measurable disease,. ) oral cavity, oropharynx, hypopharynx,
glottic and supraglottic laryngeal cancers for Arm B of the study.

4. Subject, age ≥ 18 years.

5. Performance Status (ECOG) 0-1

6. No previous therapy for the tumor, including chemotherapy, radiation therapy,
immunotherapy, EGFR targeted therapy, src directed therapies or investigational

7. Adequate Organ Function.

- Total bilirubin

- AST and ALT < 2.5 x ULN < 1.5 x ULN

- Alkaline phosphatase < 2.5 x ULN

- Hepatic enzymes (AST, ALT) < 2.5 times the institutional ULN.

- Serum Na, K+, Mg2+, Phosphate and Ca2+

- Serum Creatinine clearance > 60 ml/min. ≥ lower limit of normal (LLN).

- Hemoglobin, neutrophil count, platelets, PT, PTT all Grade 0-1.

- ANC > 1,500/mL

- Platelets > 100,000 mL

8. Concomitant medications

- Patient agrees to discontinue St. Johns Wort, proton pump inhibitors, H2
blockers, aspirin and NSAIDS while receiving dasatinib therapy.

- Patient agrees that IV and po bisphosphonates will be withheld for the first 8
weeks of dasatinib therapy due to risk of hypocalcemia.

9. Women of childbearing potential (WOCBP) must have:

- A negative serum or urine pregnancy test (sensitivity ≤ 25IU HCG/L) within 72 hours
prior to the start of study drug administration.

10. Persons of reproductive potential must agree to use and utilize an adequate method of
contraception throughout treatment and for at least 4 weeks after study drug is

11. Ability to understand and willingness to sign a written informed consent, including a
HIPAA form according to institutional guidelines.

Exclusion Criteria:

1. Any prior radiation above the clavicles

2. Prior head and neck cancer. Any other prior invasive malignancy if disease free
interval is < 3 years. Nonmelanomatous carcinomas of the skin and in situ cervical
dysplasia are allowed if completely resected within three year interval or can be
completely resected prior to starting treatment.

3. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to cetuximab, dasatinib or other agents used in study.

4. Gastrointestinal tract disease resulting in an inability to take or absorb oral or
enteral medication.

5. Concurrent medical condition which may increase the risk of toxicity, including:

- Pleural or pericardial effusion of any grade.

- Cardiac Symptoms; any of the following should be considered for exclusion:

- Uncontrolled angina, congestive heart failure or MI within (6 months).

- Diagnosed congenital long QT syndrome.

- 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).

6. Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to
protocol treatment.

7. 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).

- Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding.

8. Concomitant Medications, any of the following should be considered for exclusion:

1. Category I drugs that are generally accepted to have a risk of causing Torsades
de Pointes including: (Patients must discontinue drug 7 days prior to starting
dasatinib) quinidine, procainamide, disopyramide amiodarone, sotalol, ibutilide,
dofetilide erythromycin, clarithromycin chlorpromazine, haloperidol,
mesoridazine, thioridazine, pimozide cisapride, bepridil, droperidol, methadone,
arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine,
sparfloxacin, lidoflazine.

2. The concomitant use of H2 blockers or proton pump inhibitors with dasatinib is
not recommended. The use of antacids should be considered in place of H2
blockers or proton pump inhibitors in patients receiving dasatinib therapy. If
antacid therapy is needed, the antacid dose should be administered at least 2
hours prior to or 2 hours after the dose of dasatinib.

9. Patient may not be receiving any prohibited CYP3A4 inhibitors. Refer to section 10
for other concomitant medications you may wish to prohibit based on disease/patient

10. Women who:

- are unwilling or unable to use an acceptable method to avoid pregnancy for the
entire study period and for at least 4 weeks after cessation of study drug, or

- have a positive pregnancy test at baseline, or

- are pregnant or breastfeeding

11. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (e.g., infectious) illness.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase I is Efficacy and Safety. Phase II will be Tumor Response

Outcome Time Frame:

Phase I will enroll over 6 months

Safety Issue:


Principal Investigator

Shanthi Marur, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Johns Hopkins Universtiy


United States: Food and Drug Administration

Study ID:




Start Date:

June 2009

Completion Date:

January 2016

Related Keywords:

  • Head and Neck Cancer
  • Dasatinib
  • Cetuximab
  • Cisplatin
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms



Ohio State University Medical Center Columbus, Ohio  43210
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Baltimore, Maryland  21231