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A Phase 2 Study of Dasatinib in Head and Neck Squamous Cell Carcinoma


Phase 2
18 Years
N/A
Not Enrolling
Both
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

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Trial Information

A Phase 2 Study of Dasatinib in Head and Neck Squamous Cell Carcinoma


PRIMARY OBJECTIVE:

I. To determine the 12-week progression-free survival rate and the objective response rate,
as measured by 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 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 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 LC/MS assay, ELISA, and protein multiplex
immunoassay. Paraffin-embedded tumor tissue samples are analyzed for EMS1 gene amplification
and cortactin expression levels by FISH and IHC and apoptosis by TUNEL assay.

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


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)

- 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

- 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 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

- 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome 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.

Outcome Time Frame:

At 12-weeks

Safety Issue:

No

Principal Investigator

Vassiliki Papadimitrakopoulou

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00227

NCT ID:

NCT00507767

Start Date:

July 2007

Completion Date:

Related Keywords:

  • 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
  • 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

Name

Location

M D Anderson Cancer CenterHouston, Texas  77030