Dasatinib in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

This study has been terminated.
(Study stopped for futility.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00507767
First received: July 26, 2007
Last updated: November 1, 2013
Last verified: November 2013
  Purpose

Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase II trial is studying how well dasatinib works in treating patients with recurrent or metastatic head and neck cancer.


Condition Intervention Phase
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
Recurrent Metastatic Squamous Neck Cancer With Occult Primary
Recurrent Salivary Gland Cancer
Recurrent Squamous Cell Carcinoma of the Hypopharynx
Recurrent Squamous Cell Carcinoma of the Larynx
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Nasopharynx
Recurrent Squamous Cell Carcinoma of the Oropharynx
Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Recurrent Verrucous Carcinoma of the Larynx
Recurrent Verrucous Carcinoma of the Oral Cavity
Salivary Gland Squamous Cell Carcinoma
Stage IV Salivary Gland Cancer
Stage IV Squamous Cell Carcinoma of the Hypopharynx
Stage IV Squamous Cell Carcinoma of the Larynx
Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Stage IV Squamous Cell Carcinoma of the Oropharynx
Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IV Verrucous Carcinoma of the Larynx
Stage IV Verrucous Carcinoma of the Oral Cavity
Untreated Metastatic Squamous Neck Cancer With Occult Primary
Drug: dasatinib
Procedure: laboratory biomarker analysis
Procedure: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Dasatinib in Head and Neck Squamous Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Number of Participants With Progression-free Survival at 12-weeks [ Time Frame: At 12-weeks ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) is defined as stable disease or better. Participants who have received at least one dose of dasatinib and who die or leave the study before 12 weeks will be counted as having progressive disease.


Enrollment: 15
Study Start Date: July 2007
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (dasatinib)
Dasatinib 100 mg orally or by percutaneous gastrostomy tube twice daily on days 1-28.
Drug: dasatinib
100 mg given orally (PO) or by percutaneous gastrostomy tube twice a day, 28-day cycles.
Procedure: laboratory biomarker analysis
Correlative study
Procedure: pharmacological study
Correlative study

Detailed Description:

PRIMARY OBJECTIVE:

I. To determine the 12-week progression-free survival rate and the objective response rate, as measured by Response Evaluation Criteria in Solid Tumors (RECIST criteria), in patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with dasatinib.

SECONDARY OBJECTIVES:

I. To define metabolic response rate by positron emissions test (PET) scan at 0, 8, and 12 weeks.

II. To define overall survival distribution from initiation of dasatinib.

III. To define duration of response.

IV. To determine if there is a correlation between clinical benefit from dasatinib (defined as disease response or stabilization) and pharmacokinetics (PK), pharmacodynamics (pSrc expression in platelets), or changes in serum levels of cytokines, growth factors, and growth factor receptors relevant to the Src signaling pathway.

V. To examine the relationship between clinical benefit and EMS1 gene amplification and cortactin expression levels in tumor tissue prior to therapy and the modulation of cortactin levels by treatment (if post-treatment biopsy available).

VI. To compare the effects of dasatinib on apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay using pre- vs post-treatment tumor tissue biopsy samples.

VII. To assess the tolerability of dasatinib in this patient population.

VIII. To describe the PK profile and relative bioavailability of dasatinib suspension in patients receiving the drug through percutaneous gastrostomy tube.

IX. To descriptively assess safety, toxicity, and efficacy of dasatinib crushed and administered by feeding tube.

OUTLINE: Patients receive dasatinib orally or by percutaneous gastrostomy tube twice daily on days 1-28.

Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically for pharmacokinetic, pharmacodynamic, and biomarker correlative studies. Techniques used include Liquid chromatography-mass spectrometry (LC-MS) assay, enzyme-linked immunosorbant assay (ELISA), and protein multiplex immunoassay. Paraffin-embedded tumor tissue samples are analyzed for EMS1 gene amplification and cortactin expression levels by Fluorescence in situ hybridization (FISH) and Immunohistochemistry (IHC) and apoptosis by TUNEL assay.

After completion of study treatment, patients are followed for at least 4 weeks.

  Eligibility

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

Inclusion Criteria:

  • Brain metastases allowed provided the patient does not require anticonvulsants or corticosteroids OR has been off them for at least 7 days prior to study entry (Brain metastases must have been treated with cranial irradiation > 4 weeks ago OR did not require cranial irradiation at that time)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelet count >= 100,000/mcL
  • Hemoglobin >= 9.0 g/dL
  • Total bilirubin =< 1.5 times upper limit of normal (ULN)
  • Albumin >= 2.5 g/dL
  • aspartate aminotransferase and alanine aminotransferase (AST and ALT) =< 1.5 times ULN
  • Creatinine =< 3 mg/dL
  • Oxygen saturation >= 92% on room air
  • All females of childbearing potential must have a negative pregnancy test within 72 hours prior to enrolling in the study
  • All sexually active females of child-bearing potential and all sexually active males with sexual partners of child-bearing potential should practice contraception (e.g., barrier, hormonal, IUD) or sexual abstinence during the study and for 2 months following completion of study therapy
  • Recovered from prior therapy
  • At least 7 days since any of the following:

    • CYP3A4 inhibitors
    • Agents with proarrhythmic potential
    • Anticoagulants or medications that inhibit platelet function, including therapeutic warfarin or heparin
  • Histologically proven squamous cell carcinoma of the head and neck meeting one of the following criteria:

    • Recurrent disease after surgery and/or radiotherapy or chemoradiotherapy
    • Metastatic disease
  • Measurable disease as defined by RECIST criteria
  • Paraffin embedded tumor tissue that is appropriate for IHC and FISH analysis must be available OR patient must be amenable to biopsy to obtain tissue for the study
  • No pleural effusion

Exclusion Criteria:

  • Pregnant or nursing
  • History of uncontrolled or severe medical disease which could compromise study participation, including the following:

    • Uncontrolled diabetes (fasting blood glucose > 200 mg/dL)
    • Uncontrolled hypertension (systolic blood pressure (BP)) > 160 mm Hg or diastolic BP > 100 mm Hg)
    • Severe infection (bacterial infection requiring IV antibiotics)
    • HIV
  • History of uncontrolled or severe medical disease which could compromise study participation, including the following:

    • Angina at rest
    • New York Heart Association (NYHA) class III or IV congestive heart failure
    • Ventricular arrhythmias requiring treatment
    • Neuropathy > grade 2
  • Echocardiogram less than institutional normal (in patients with a history of congestive heart failure, symptoms of congestive heart failure, or clinical evidence suggesting impaired cardiac function)
  • Chemotherapy (6 weeks for nitrosoureas or mitomycin C) or palliative radiotherapy for recurrent and/or metastatic disease within the past 3 weeks
  • Concurrent chemoradiotherapy within the past 6 weeks or failure to recover to at least grade1 from therapy completed more than 4 weeks ago
  • Concurrent treatment with any medications or substances that are potent inhibitors or inducers of CYP3A4
  • Concurrent agents with proarrhythmic potential
  • Other concurrent anti-neoplastic agents (i.e., cytotoxic chemotherapy, immunotherapy, radiotherapy, or investigational therapy) used to treat the primary disease [Local radiotherapy (excluding radiotherapy to the target lesion) involving a small radiation field for supportive reasons allowed]
  • Any other concurrent investigational agents
  • Bisphosphonate therapy during the first 8 weeks of study treatment
  • Clinically significant cardiovascular disease, including the following:

    • Myocardial infarction or ventricular tachyarrhythmia within the past 6 months
    • Prolonged QTc > 480 msec (Fridericia correction)
    • Major conduction abnormality (unless a cardiac pacemaker is present)
  • Received > 1 prior chemotherapeutic regimen for recurrent or metastatic disease
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00507767

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Vassiliki Papadimitrakopoulou, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00507767     History of Changes
Obsolete Identifiers: NCT00513227
Other Study ID Numbers: NCI-2009-00227, NCI-2009-00227, CDR0000559148, 7815, 2006-0571, 2006-0571, N01CM62202
Study First Received: July 26, 2007
Results First Received: April 18, 2012
Last Updated: November 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Laryngeal Diseases
Carcinoma, Verrucous
Neoplasms, Unknown Primary
Salivary Gland Neoplasms
Hypopharyngeal Neoplasms
Laryngeal Neoplasms
Paranasal Sinus Neoplasms
Oropharyngeal Neoplasms
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Mouth Neoplasms
Mouth Diseases
Stomatognathic Diseases
Salivary Gland Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Respiratory Tract Neoplasms

ClinicalTrials.gov processed this record on April 23, 2014