A Study of Dasatinib, Cetuximab and Radiation With or Without Cisplatin in HNSCC

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00882583
First received: April 15, 2009
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

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.

Condition Intervention Phase
Head and Neck Cancer
Drug: Cetuximab
Drug: Dasatinib
Drug: Cisplatin
Radiation: Radiation Therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Phase I is Efficacy and Safety. Phase II will be Tumor Response [ Time Frame: Phase I will enroll over 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Phase I Tumor Response. Phase II Time on Treatment [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 98
Study Start Date: June 2009
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A

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).

Drug: Cetuximab
single agent cetuximab loading dose of 400mg/m2 on day1, cetuximab maintenance dose 250mg/m2 on day 8
Other Name: Erbitux
Drug: Dasatinib
Oral Dasatinib Days 8 through 64.
Other Names:
  • Sprycel
  • BMS-354825
Radiation: Radiation Therapy
Standard Radiation Therapy.
B

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.

Drug: Cetuximab
single agent cetuximab loading dose of 400mg/m2 on day1, cetuximab maintenance dose 250mg/m2 on day 8
Other Name: Erbitux
Drug: Dasatinib
Oral Dasatinib Days 8 through 64.
Other Names:
  • Sprycel
  • BMS-354825
Drug: Cisplatin
Q 3 weeks (Days 15, 36 and 57): +/- 3 Days
Other Names:
  • Cisplatinum
  • cis-diamminedichloroplatinum(II) (CDDP)
  • Platinol
  • Platin
Radiation: Radiation Therapy
Standard Radiation Therapy.

Detailed 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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00882583

Locations
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21287
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Bristol-Myers Squibb
Investigators
Principal Investigator: Shanthi Marur, MD Johns Hopkins Universtiy
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00882583     History of Changes
Other Study ID Numbers: J08101, CA180123
Study First Received: April 15, 2009
Last Updated: June 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
HNSCC
Dasatinib
Cetuximab
Cisplatin

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms
Neoplasms by Site
Cetuximab
Cisplatin
Dasatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014