Overview

This trial is active, not recruiting.

Condition head and neck cancer
Treatments cetuximab, dasatinib, cisplatin, radiation therapy
Phase phase 1/phase 2
Targets BCR-ABL, EGFR
Sponsor Sidney Kimmel Comprehensive Cancer Center
Collaborator Bristol-Myers Squibb
Start date June 2009
End date January 2016
Trial size 98 participants
Trial identifier NCT00882583, CA180123, J08101

Summary

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

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Other)
In both Cohort A and B, there will be an initial "run-in period" of single agent cetuximab loading dose of 400mg/m2 on day1, cetuximab maintenance dose 250mg/m2 on day 8 and oral dasatinib from day 8-14. Cohort A will consist of patients with AJCC stage II (T2N0) and III (T1-2N1) SCCHN of oral cavity, oropharynx, T2N0 hypopharynx, T2N0-1 supraglottic larynx. Treatment will be dasatinib in combination with cetuximab and radiation therapy (RT).
cetuximab Erbitux
single agent cetuximab loading dose of 400mg/m2 on day1, cetuximab maintenance dose 250mg/m2 on day 8
dasatinib Sprycel
Oral Dasatinib Days 8 through 64.
radiation therapy
Standard Radiation Therapy.
(Other)
In both Cohort A and B, there will be an initial "run-in period" of single agent cetuximab loading dose of 400mg/m2 on day1, cetuximab maintenance dose 250mg/m2 on day 8 and oral dasatinib from day 8-14. Cohort B will include patients with AJCC stage III (T3N0-1) and IV (T1-4N2-3M0, T4N0-1M0) squamous cell carcinoma of Oral Cavity, Oropharynx, Hypopharynx, and Larynx. Treatment will be daily dasatinib, in combination with q 3 week cisplatin, weekly cetuximab and RT.
cetuximab Erbitux
single agent cetuximab loading dose of 400mg/m2 on day1, cetuximab maintenance dose 250mg/m2 on day 8
dasatinib Sprycel
Oral Dasatinib Days 8 through 64.
cisplatin Cisplatinum
Q 3 weeks (Days 15, 36 and 57): +/- 3 Days
radiation therapy
Standard Radiation Therapy.

Primary Outcomes

Measure
Phase I is Efficacy and Safety. Phase II will be Tumor Response
time frame: Phase I will enroll over 6 months

Secondary Outcomes

Measure
Phase I Tumor Response. Phase II Time on Treatment
time frame: 6 months

Eligibility Criteria

Male or female participants at least 18 years old.

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, T4N0-1M0) oral cavity, oropharynx, hypopharynx, glottic and supraglottic laryngeal cancers for Arm B of the study. 3. Patients must have measurable disease,. 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 agents. 7. Adequate Organ Function. - Total bilirubin ≤ 1.5 x ULN - AST and ALT ≤ 2.5 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+ ≥ lower limit of normal (LLN). - Serum Creatinine clearance ≥ 60 ml/min. - 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 stopped. 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 population. 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.

Additional Information

Official title 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)
Principal investigator Shanthi Marur, MD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2014.
Information provided to ClinicalTrials.gov by Sidney Kimmel Comprehensive Cancer Center.