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A Phase I/II Study of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, OSI-774, in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage III Squamous Cell Carcinoma of the Nasopharynx, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage III Verrucous Carcinoma of the Larynx, Stage III Verrucous Carcinoma of the Oral Cavity, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx, 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 Verrucous Carcinoma of the Larynx, Stage IVA Verrucous Carcinoma of the Oral Cavity, 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 Verrucous Carcinoma of the Larynx, Stage IVB Verrucous Carcinoma of the Oral Cavity, 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 Verrucous Carcinoma of the Larynx, Stage IVC Verrucous Carcinoma of the Oral Cavity, Tongue Cancer, Untreated Metastatic Squamous Neck Cancer With Occult Primary

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Trial Information

A Phase I/II Study of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, OSI-774, in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck


PRIMARY OBJECTIVES:

I. Determine MTD and toxicity of combination of EGFR inhibitor (OSI-774), docetaxel, and
radiation. (Phase I) II. Pharmacokinetic profile of OSI-774 alone and in combination with
docetaxel. (Phase I) III. Determine the time to progression of the combination of EGFR
inhibitor (OSI-774), docetaxel and radiation. (Phase II)

SECONDARY OBJECTIVES:

I. Determine the overall and complete response rate of this combination. (Phase I) II.
Determine overall, disease free, and progression free survival of this combination. (Phase
I) III. Determine objective response rate, locoregional control rate, duration of response,
patterns of failure, overall survival and toxicities of this combination. (Phase II) IV.
Determine the pharmacokinetic profile of erlotinib alone and in combination with docetaxel.
(Phase II) V. Determine the effect of treatment and dose of treatment on biologic correlates
in tumor tissue and/or surrounding mucosa (Phase II)

- EGFR expression and phosphorylation status

- Serum markers of angiogenic activity VEGF, sVEGFR-2, sKIT, ICAM, PDGF

- Fluorescence in situ hybridization (FISH) for EGFR, ERBB2, PDGFR-β for gene
amplification

- DNA-sequencing of EGFR and ERBB2 genes from DNA extracted from pretreatment biopsy
material for mutation screening

- Gene expression profiling on pre-treatment biopsy material to identify predictors of
response to treatment

- Apoptosis (TUNEL assay)

- Ki67 (nuclear proliferation antigen).

OUTLINE: This is a dose-escalation study of erlotinib and docetaxel.

Patients receive oral erlotinib alone daily on weeks 1 and 2. Patients then receive oral
erlotinib daily beginning on day 1 and docetaxel IV over 1 hour on day 3 of weeks 3-9.
Patients also undergo radiotherapy once daily 5 days a week on weeks 3-9. Patients continue
erlotinib for up to 2 years in the absence of disease progression or unacceptable toxicity.
Patients who had N2 or greater cervical lymph node involvement at baseline or have residual
neck adenopathy after chemoradiotherapy undergo neck dissection 6-8 weeks after completion
of chemoradiotherapy. Erlotinib is held for 1 week before planned surgery and until healing
is complete.

Cohorts of 3-6 patients receive escalating doses of erlotinib and docetaxel until the MTD is
determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients
experience dose-limiting toxicity.

Patients are followed every 16 weeks for 1 year after completion of erlotinib, every 24
weeks for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study.


Inclusion Criteria:



- Patients must have histologically or cytologically confirmed locally advanced (stage
III or IV) squamous cell carcinoma of the head and neck without distant metastatic
disease

- No prior chemotherapy, radiation therapy, or investigational anti-tumor drug

- Measurable disease within 4 weeks prior to registration according to the recommended
RECIST response criteria

- ECOG performance status =< 2 (Karnofsky >= 60%)

- Life expectancy of greater than 12 weeks

- Absolute neutrophil count >= 1,500/ul

- Platelets >= 100,000/ul

- Hemoglobin >= 10 mg/dL

- Total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) =< 5 x ULN when alkaline phosphatase is =< ULN

- Alkaline phosphatase =< 5 x ULN when AST or ALT =< ULN

- Prothrombin time within normal institutional limits

- Creatinine within normal institutional limits or creatinine clearance >= 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

- No clinically significant heart disease (including NYHA class III or IV heart
disease, significant arrhythmias requiring medication, symptomatic coronary artery
disease, myocardial infarction within the previous six months, second or third degree
heart block or bundle branch block)

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control) prior to study entry and for the
duration of study participation; men and women of childbearing potential must be
willing to consent to using effective contraception while on treatment and for at
least 3 months thereafter; women of childbearing potential must have a negative
pregnancy test; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately

- Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

- All histologies other than squamous cell carcinoma

- Salivary gland and paranasal sinus squamous cell carcinoma

- Patients who have had prior chemotherapy or radiotherapy

- Patients may not be receiving any other investigational agents

- Patients with known brain metastases or direct cerebral invasion by tumor should be
excluded from this clinical trial because of their poor prognosis and because they
often develop progressive neurologic dysfunction that would confound the evaluation
of neurologic and other adverse events; patients with intracranial extension (but
without cerebral involvement) may still be eligible to participate

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to OSI-774 or docetaxel, including other drugs formulated with
polysorbate 80

- No pre-existing peripheral neuropathy >= grade 2

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated on this protocol

- HIV positive patients are excluded from participation

- Patients with history of any other malignancy (except squamous cell or basal cell
cancer of the skin or CIS of cervix) are ineligible unless a period of 5 years has
elapsed since treatment of the previous cancer and the patient has remained
continuously disease free

- Patients who are felt to be poorly compliant

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

MTD defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity assessed using Common Toxicity Criteria (CTC) version 3.0 (Phase I)

Outcome Time Frame:

9 weeks

Safety Issue:

Yes

Principal Investigator

Panayiotis (Panos) Savvides

Investigator Role:

Principal Investigator

Investigator Affiliation:

Case Western Reserve University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-03113

NCT ID:

NCT00049283

Start Date:

September 2002

Completion Date:

Related Keywords:

  • Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
  • Stage III Squamous Cell Carcinoma of the Hypopharynx
  • Stage III Squamous Cell Carcinoma of the Larynx
  • Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage III Squamous Cell Carcinoma of the Nasopharynx
  • Stage III Squamous Cell Carcinoma of the Oropharynx
  • Stage III Verrucous Carcinoma of the Larynx
  • Stage III Verrucous Carcinoma of the Oral Cavity
  • Stage IV Squamous Cell Carcinoma of the Hypopharynx
  • Stage IV Squamous Cell Carcinoma of the Nasopharynx
  • 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 Verrucous Carcinoma of the Larynx
  • Stage IVA Verrucous Carcinoma of the Oral Cavity
  • 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 Verrucous Carcinoma of the Larynx
  • Stage IVB Verrucous Carcinoma of the Oral Cavity
  • 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 Verrucous Carcinoma of the Larynx
  • Stage IVC Verrucous Carcinoma of the Oral Cavity
  • Tongue Cancer
  • Untreated Metastatic Squamous Neck Cancer With Occult Primary
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Neoplasms, Squamous Cell
  • Head and Neck Neoplasms
  • Laryngeal Diseases
  • Tongue Neoplasms
  • Carcinoma, Verrucous
  • Neoplasms, Unknown Primary
  • Hypopharyngeal Neoplasms
  • Laryngeal Neoplasms
  • Oropharyngeal Neoplasms
  • Nasopharyngeal Neoplasms

Name

Location

Case Western Reserve UniversityCleveland, Ohio  44106