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

Primary Purpose

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Salivary Gland Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
dasatinib
pharmacological study
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patient has histologically proven squamous cell carcinoma of the head and neck that is recurrent after surgery and/or radiation therapy or chemoradiation therapy or is metastatic and disease must be measurable by RECIST criteria
  • Patients must have measurable disease as defined by RECIST criteria
  • Patients have received =< 1 prior chemotherapeutic regimen for recurrent or metastatic disease
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin (Hgb) >= 9.0 g/dL
  • Total bilirubin =< 1.5 X upper limit of normal
  • Albumin >= 2.5 g/dL
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 1.5 X upper limit of normal
  • Creatinine =< 3 mg/dl
  • Paraffin embedded tumor tissue that is appropriate for immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) analysis must be available or patient must be amenable to biopsy to obtain tissue for the study
  • Ability to understand and the willingness to sign a written informed consent document
  • Patient must not be pregnant or breastfeeding; 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, intrauterine device [IUD]) or sexual abstinence while in the study and for two months following completion of therapy
  • Brain metastases permitted provided the patient does not require anticonvulsants or corticosteroids, or has been off them at least 7 days; patients with brain metastases must be either > 4 weeks beyond cranial irradiation or must be felt not to require it at that time
  • The patient's O2 saturation must be >= 92% on room air

Exclusion Criteria:

  • Chemotherapy or palliative radiotherapy for recurrent and/or metastatic disease within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or failure to recover to at least grade 1 from adverse events due to agents administered more than 4 weeks earlier; concomitant chemoradiation therapy within 6 weeks prior to entering the study or failure to recover to at least grade 1 from adverse events due to agents administered more than 4 weeks earlier
  • Other anti-neoplastic agents, i.e., cytotoxic chemotherapy, immunotherapy, radiotherapy or investigational therapy, used to treat the primary disease will not be allowed during the study; local radiation (excluding radiotherapy to the target lesion) for supportive reasons involving a small radiation field may be allowed
  • Patient has a history of uncontrolled or severe medical disease which could compromise participation in the study such as uncontrolled diabetes (fasting blood glucose > 200 mg/dl), uncontrolled hypertension (systolic blood pressure [BP] > 160 or diastolic BP > 100 mmHg), severe infection (bacterial infection requiring intravenous [IV] antibiotics or human immunodeficiency virus [HIV]), angina at rest, congestive heart failure New York Heart Association (NYHA) class III or IV, ventricular arrhythmias requiring therapy, myocardial infarction within 6 months, > grade 2 neuropathy
  • Patients may not be receiving any other investigational agents
  • Patients who require concurrent treatment with any medications or substances that are potent inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible; efforts should be made to switch patients with gliomas or brain metastases who are taking enzyme-inducing anticonvulsant agents to other medications
  • Echocardiogram less than institutional normal measured by echocardiogram for subjects with history of congestive heart failure, symptoms of congestive heart failure, clinical evidence suggesting impaired cardiac function
  • Patients may not have any clinically significant cardiovascular disease including the following:

    • Myocardial infarction or ventricular tachyarrhythmia within 6 months
    • Prolonged correct QT interval (QTc) > 480 msec (Fridericia correction)
    • Major conduction abnormality (unless a cardiac pacemaker is present)
  • Pregnant women and women who are currently breast-feeding may not participate in this study; all women of childbearing potential must have a negative pregnancy test within 72 hours prior to enrolling in the study; postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential
  • Patients having pleural effusion

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (dasatinib)

Arm Description

Patients receive dasatinib PO or via PEG tube BID. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Number of Participants With Progression-free Survival at 12-weeks
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.

Secondary Outcome Measures

Full Information

First Posted
July 26, 2007
Last Updated
September 17, 2014
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00507767
Brief Title
Dasatinib in Treating Patients With Recurrent or Metastatic Head and Neck Cancer
Official Title
A Phase 2 Study of Dasatinib in Head and Neck Squamous Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
February 2010 (Actual)
Study Completion Date
February 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase II trial studies how well dasatinib works in treating patients with head and neck cancer that has come back or spread to other areas of the body. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES: 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 emission tomography (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, pharmacodynamics (phosphorylated Src [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 mammary tumor and squamous cell carcinoma-associated protein (EMS1) gene amplification and cortactin expression levels in tumor tissue prior to therapy and the modulation of cortactin levels by treatment. VI. To compare the effects of dasatinib on apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in tumor tissues comparing pre- and post-treatment biopsies. VII. To assess the tolerability of dasatinib in this patient population. VIII. To describe the pharmacokinetic (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 (PO) or via percutaneous gastrostomy (PEG) tube twice daily (BID). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for at least 4 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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 Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IVA Salivary Gland Cancer, Stage IVA Squamous Cell Carcinoma of the Larynx, Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVA Verrucous Carcinoma of the Larynx, Stage IVA Verrucous Carcinoma of the Oral Cavity, Stage IVB Salivary Gland Cancer, Stage IVB Squamous Cell Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Oropharynx, Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVB Verrucous Carcinoma of the Larynx, Stage IVB Verrucous Carcinoma of the Oral Cavity, Stage IVC Salivary Gland Cancer, Stage IVC Squamous Cell Carcinoma of the Larynx, Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVC Squamous Cell Carcinoma of the Oropharynx, Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVC Verrucous Carcinoma of the Larynx, Stage IVC Verrucous Carcinoma of the Oral Cavity, Tongue Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (dasatinib)
Arm Type
Experimental
Arm Description
Patients receive dasatinib PO or via PEG tube BID. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
dasatinib
Other Intervention Name(s)
BMS-354825, Sprycel
Intervention Description
Given PO or via PEG tube
Intervention Type
Procedure
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Intervention Type
Procedure
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Number of Participants With Progression-free Survival at 12-weeks
Description
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.
Time Frame
At 12-weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient has histologically proven squamous cell carcinoma of the head and neck that is recurrent after surgery and/or radiation therapy or chemoradiation therapy or is metastatic and disease must be measurable by RECIST criteria Patients must have measurable disease as defined by RECIST criteria Patients have received =< 1 prior chemotherapeutic regimen for recurrent or metastatic disease Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Leukocytes >= 3,000/mcL Absolute neutrophil count >= 1,500/mcL Platelets >= 100,000/mcL Hemoglobin (Hgb) >= 9.0 g/dL Total bilirubin =< 1.5 X upper limit of normal Albumin >= 2.5 g/dL Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 1.5 X upper limit of normal Creatinine =< 3 mg/dl Paraffin embedded tumor tissue that is appropriate for immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) analysis must be available or patient must be amenable to biopsy to obtain tissue for the study Ability to understand and the willingness to sign a written informed consent document Patient must not be pregnant or breastfeeding; 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, intrauterine device [IUD]) or sexual abstinence while in the study and for two months following completion of therapy Brain metastases permitted provided the patient does not require anticonvulsants or corticosteroids, or has been off them at least 7 days; patients with brain metastases must be either > 4 weeks beyond cranial irradiation or must be felt not to require it at that time The patient's O2 saturation must be >= 92% on room air Exclusion Criteria: Chemotherapy or palliative radiotherapy for recurrent and/or metastatic disease within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or failure to recover to at least grade 1 from adverse events due to agents administered more than 4 weeks earlier; concomitant chemoradiation therapy within 6 weeks prior to entering the study or failure to recover to at least grade 1 from adverse events due to agents administered more than 4 weeks earlier Other anti-neoplastic agents, i.e., cytotoxic chemotherapy, immunotherapy, radiotherapy or investigational therapy, used to treat the primary disease will not be allowed during the study; local radiation (excluding radiotherapy to the target lesion) for supportive reasons involving a small radiation field may be allowed Patient has a history of uncontrolled or severe medical disease which could compromise participation in the study such as uncontrolled diabetes (fasting blood glucose > 200 mg/dl), uncontrolled hypertension (systolic blood pressure [BP] > 160 or diastolic BP > 100 mmHg), severe infection (bacterial infection requiring intravenous [IV] antibiotics or human immunodeficiency virus [HIV]), angina at rest, congestive heart failure New York Heart Association (NYHA) class III or IV, ventricular arrhythmias requiring therapy, myocardial infarction within 6 months, > grade 2 neuropathy Patients may not be receiving any other investigational agents Patients who require concurrent treatment with any medications or substances that are potent inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible; efforts should be made to switch patients with gliomas or brain metastases who are taking enzyme-inducing anticonvulsant agents to other medications Echocardiogram less than institutional normal measured by echocardiogram for subjects with history of congestive heart failure, symptoms of congestive heart failure, clinical evidence suggesting impaired cardiac function Patients may not have any clinically significant cardiovascular disease including the following: Myocardial infarction or ventricular tachyarrhythmia within 6 months Prolonged correct QT interval (QTc) > 480 msec (Fridericia correction) Major conduction abnormality (unless a cardiac pacemaker is present) Pregnant women and women who are currently breast-feeding may not participate in this study; all women of childbearing potential must have a negative pregnancy test within 72 hours prior to enrolling in the study; postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential Patients having pleural effusion
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vassiliki Papadimitrakopoulou
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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