Erlotinib and Cisplatin in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib with cisplatin may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining erlotinib and cisplatin in treating patients who have recurrent or metastatic head and neck cancer.

Detailed Description
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OBJECTIVES: Determine the objective response rate in patients with recurrent or metastatic squamous cell cancer of the head and neck treated with erlotinib and cisplatin. Determine the stable disease rates, duration of response, progression-free survival, median survival, and overall survival of patients treated with this regimen. Determine the safety and tolerability of this regimen in these patients. Determine the relationship between clinical, pharmacokinetic, and pharmacodynamic effects of this regimen in these patients. Correlate baseline and post-treatment levels of epidermal growth factor receptor, its downstream signaling components, and markers of angiogenesis and apoptosis in tumor and skin biopsies with clinical outcome in patients treated with this regimen. OUTLINE: This is a dose-escalation, multicenter study. Patients receive oral erlotinib once daily on days -6 to 21 for the first course only and cisplatin IV over 60 minutes on day 1. For the second and subsequent courses, patients receive oral erlotinib once daily on days 1-21 and cisplatin as in course 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease after 6 courses may continue to receive erlotinib alone until disease progression. Cohorts of 3-6 patients receive escalating doses of erlotinib and cisplatin until the maximum tolerated dose (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. At least 6 patients are treated at the MTD. Patients are followed every 3 months. PROJECTED ACCRUAL: A maximum of 43 patients will be accrued for this study within 18 months.

Official Title
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A Phase I/II Study Of OSI-774 In Combination With Cisplatin In Patients With Recurrent Or Metastatic Squamous Cell Cancer Of The Head And Neck

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: erlotinib hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma of the head and neck All primary sites, including oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, and paranasal sinus Recurrent, unresectable, and/or metastatic disease At least 1 measurable lesion At least 20 mm with conventional techniques OR at least 10 mm with spiral CT scan Lesions accessible for biopsy Tumor specimen available for evaluation of epidermal growth factor receptor (EGFR) expression No known brain metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 OR Karnofsky 60-100% Life expectancy: More than 12 weeks Hematopoietic: WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.25 times upper limit of normal (ULN) AST and ALT no greater than 2.5 times ULN Renal: Creatinine normal OR Creatinine clearance at least 60 mL/min Cardiovascular: No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Gastrointestinal: No gastrointestinal tract disease resulting in malabsorption No requirement for IV alimentation No active peptic ulcer disease Inability to swallow tablets or silicon-based G-tubes allowed Ophthalmic: No abnormalities of the cornea based on history (e.g., dry eye syndrome or Sjogren's syndrome) No congenital abnormality (e.g., Fuch's dystrophy) No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose) No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test) Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 5 years except carcinoma in situ of the cervix, nonmelanoma skin cancer, or second primary squamous cell cancer originating from the head and neck No grade 2 or greater residual ototoxicity or neuropathy from prior platinum-based therapy No significant traumatic injury within the past 21 days No other concurrent uncontrolled illness No ongoing or active infection No psychiatric illness or social situation that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for recurrent or metastatic disease Prior platinum-based chemotherapy with radiotherapy or platinum-based induction chemotherapy allowed At least 6 months since prior chemotherapy Endocrine therapy: Not specified Radiotherapy: See Chemotherapy At least 4 weeks since prior radiotherapy (except low-dose, limited-fraction palliative non-myelosuppressive radiotherapy [e.g., involving less than 20% of functioning bone marrow using 800 cGy in 1 fraction or 2,000 cGy in 5 fractions]) and recovered No prior radiotherapy to target lesion unless there is evidence of disease progression Surgery: See Disease Characteristics At least 21 days since prior major surgery No prior surgical procedure affecting gastrointestinal absorption Other: No prior EGFR-targeting therapies No prior investigational agents for recurrent or metastatic disease No concurrent combination anti-retroviral therapy for HIV infection No other concurrent investigational agents No other concurrent anticancer treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OSI-774 and cisplatin<br>HNSCC patients treated in three escalating dose cohorts of daily continous oral erlotinib (OSI-774) and intermittent IV cisplatin given every 21 days | Drug: cisplatin<br> <br> Drug: erlotinib hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent metastatic squamous neck cancer occult primary, neck cancer with occult primary squamous carcinoma, stage IV squamous cell carcinoma of the lip and oral cavity, recurrent squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the nasopharynx, recurrent squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the larynx, recurrent squamous cell carcinoma of the larynx, squamous cell carcinoma of paranasal sinus and nasal cavity, recurrent squamous cell carcinoma of sinus and nasal cavity