A Phase I and Phase II Study of OSI-774 in Combination With Docetaxel in Squamous Cell Carcinoma of the Head and Neck
A Phase I and Phase II Study of OSI-774 in Combination With Docetaxel in Squamous Cell Carcinoma of the Head and Neck
Phase I/II trial to study the effectiveness of combining erlotinib with docetaxel in treating patients who have locally advanced, recurrent, or metastatic head and neck cancer. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib with docetaxel may kill more tumor cells.
OBJECTIVES:
I. Determine the maximum tolerated dose and dose-limiting toxicity of erlotinib when administered in combination with docetaxel in patients with locally advanced, metastatic, or recurrent squamous cell carcinoma of the head and neck.
II. Determine the response rate, duration of response, time to progression, and survival of patients treated with this regimen.
III. Determine the pharmacokinetics of this regimen in these patients. IV. Correlate the presence of PTEN, RB, P-Akt, p15, p16, cyclin D1, p27, and p53 genes in tumor tissue with response in patients treated with this regimen.
OUTLINE: This is a phase I, dose-escalation study of erlotinib followed by a phase II study.
PHASE I: Patients receive oral erlotinib once daily on days 1-28 and docetaxel IV over 1 hour on days 8, 15, and 22. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional cohort of 6 patients receives erlotinib at the MTD.
PHASE II: Patients receive erlotinib at the MTD and docetaxel as in phase I.
Inclusion Criteria:
Histologically or cytologically confirmed squamous cell carcinoma of the head and neck meeting 1 of the following staging criteria:
Measurable disease
No known brain metastases
Performance status - ECOG 0-2
Performance status - Karnofsky 60-100%
WBC at least 3,000/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Bilirubin normal
AST and ALT no greater than 2.5 times upper limit of normal
Creatinine normal
Creatinine clearance at least 60 mL/min
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
No severe pulmonary insufficiency, including chronic obstructive pulmonary disease, requiring oxygen (O2 saturation less than 90%) and/or increase in PaCO2 blood gas level greater than 50 mm Hg
No history of abnormality of the cornea (e.g., dry eye syndrome or Sjögren'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 (Schirmer test or similar tear production test)
Able to take oral medication
No requirement for IV alimentation
No active peptic ulcer disease
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No significant traumatic injury within the past 21 days
No prior allergic reactions to compounds of similar chemical or biological composition to study drugs
No grade 2 or greater persistent peripheral neuropathy
No other concurrent uncontrolled illness that would preclude study participation
No ongoing or active infection
No psychiatric illness or social situation that would preclude study compliance
No prior immunotherapy for head and neck cancer
No more than 1 prior chemotherapy regimen in the adjuvant or neoadjuvant setting
No more than 1 prior chemotherapy regimen for metastatic disease
No prior docetaxel (phase II only)
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
No prior hormonal therapy for head and neck cancer
Prior external beam radiotherapy allowed
At least 4 weeks since prior radiotherapy and recovered
More than 21 days since prior major surgery
No prior surgery affecting gastrointestinal absorption
No prior epidermal growth factor receptor-targeting therapy
No other concurrent investigational agents
No other concurrent anticancer therapies or agents
No concurrent combination antiretroviral therapy for HIV-positive patients