Erlotinib Hydrochloride and Radiation Therapy in Stage III-IV Squamous Cell Cancer of the Head and Neck
Condition: 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 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 Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Laryngeal Neoplasms; Oropharyngeal Neoplasms; Carcinoma, Verrucous; Squamous Cell Carcinoma of Head and Neck; Nasopharyngeal Carcinoma; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Laryngeal Diseases
Intervention: erlotinib hydrochloride; intensity-modulated radiation therapy; pharmacogenomic studies; gene expression analysis; 3-dimensional conformal radiation therapy; biopsy; pharmacological study; laboratory biomarker analysis; questionnaire administration; enzyme-linked immunosorbent assay; polymorphism analysis
Intervention description: Given orally or via gastronomy tube; IMRT will be given in 35 fractions over 7 weeks. The primary tumor and involved nodes (PTV70) will receive 2 Gy per fractions, intermediate-risk areas (PTV63) will receive 1.8 Gy per fractions, and subclinical disease sites (PTV56) will receive 1.6 Gy perfraction. The total doses will thus be 70 Gy, 63 Gy and 56 Gy, respectively.; Optional correlative studies; Correlative studies; The initial target volume encompassing the gross and subclinical disease sites will receive 2.0 Gy per fraction, five fractions a week to 54 Gy in 27 fractions in 5.4 weeks. The boost volume covering gross tumor and clinically/radiologically involved nodes will receive boost irradiation for additional 16 Gy at 2.0 Gy. The primary tumor and clinically/radiologically-involved nodes will thus receive 70 Gy in 35 fractions over 7 weeks, and uninvolved upper neck nodes will receive an elective dose of 54 Gy in 5.4 weeks.
The uninvolved lower neck nodes will receive 2.0 Gy per fraction at 3-cm depth to a total dose of 50 Gy in 25 fractions in 5.0 weeks through a matching AP or AP/PA lower neck field.; Optional correlative studies; Optional correlative studies; Optional correlative studies; Optional ancillary studies; Optional correlative studies; Optional correlative studies
Intervention MeSH terms: Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      RATIONALE: Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth. Erlotinib hydrochloride may also make tumor cells more
      sensitive to radiation therapy. Radiation therapy uses high-energy x- rays and other types of
      radiation to kill tumor cells. Giving erlotinib hydrochloride together with radiation therapy
      may be an effective treatment for patients with head and neck cancer.PURPOSE: This phase II
      trial is studying how well giving erlotinib hydrochloride together with radiation therapy
      works in treating patients with stage III-IV squamous cell cancer of the head and neck.
    

Eligibility criteria:

        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, who are not candidates or have declined definitive surgical resection or for
             administration of standard chemotherapy during radiation therapy because of any of the
             following reasons: advanced age (>= 70 years); poor ECOG performance status (2 or 3);
             significant comorbidities, as reflected by a Charlson comorbidity index score of >= 3;
             abnormal hematopoietic, hepatic or renal function; patient's decision after applicable
             standard treatment options have been offered and declined by patient

          -  No prior chemotherapy, radiation therapy, or investigational antitumor drug

          -  Measurable disease within 4 weeks prior to registration according to the recommended
             RECIST response criteria

          -  Life expectancy of greater than 12 weeks

          -  Patients must have normal hepatic function or well compensated liver disease as
             defined by the Child-Pugh classification of severity of liver disease; patients with
             hepatic impairment (total bilirubin greater than upper limit of normal [ULN] or
             well-compensated disease [Child-Pugh class A] enrolled in the trial will be closely
             monitored, especially those with total bilirubin > 3 times ULN; dosage modifications
             (therapy interruption or discontinuation) may be necessary for severe changes in liver
             function; patient management will follow the FDA-approved labeling recommendations

          -  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 paranasal sinus and nasopharyngeal squamous cell carcinoma

          -  Patients who have had prior chemotherapy or radiotherapy

          -  Patients with metastatic disease

          -  Patients with ECOG performance status of 4

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ERLOTINIB

          -  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 is currently
             disease-free from the previous cancer

          -  Patients may not be receiving any other investigational agent

          -  Pregnant women; breastfeeding should be discontinued