Cetuximab and Recombinant Interleukin-12 in Treating Patients With Squamous Cell Carcinoma of the Head and Neck That is Recurrent, Metastatic, or Cannot Be Removed by Surgery

PRIMARY OBJECTIVES:

I. To find a safe and tolerable interleukin (IL)-12 (recombinant interleukin-12) dose for use
in combination with cetuximab in patients with squamous cell carcinoma of the head and neck.
(Phase I) II. To determine the response rate to the combination of IL-12 and cetuximab.
(Phase II)

SECONDARY OBJECTIVES:

I. To characterize the immunologic effects of IL-12 when administered in combination with
cetuximab.

OUTLINE: This is a phase I, dose-escalation study of recombinant IL-12 followed by a phase II
study.

Patients receive cetuximab intravenously (IV) over 1-2 hours on day 1 and recombinant
interleukin-12 subcutaneously (SC) on days 2 and 5 beginning in course 2. Treatment repeats
every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.
Patients achieving clinical response or stable disease may continue with therapy until
disease progression.

After completion of study treatment, patients are followed up for 1 year.

Inclusion Criteria:

- Patients must have histologically-proven recurrent and/or metastatic squamous cell
carcinoma of the head and neck that is unresectable; patients in the phase II portion
of the trial must have measurable disease

- Any number of prior systemic therapies for metastatic/recurrent disease are permitted
in both the phase I and II portions of the study; patients need not have received a
prior cetuximab-based chemotherapy regimen to be eligible for this trial

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

- Life expectancy of greater than 6 months

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 times upper limit of normal

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

- The effects of IL-12 on the developing human fetus are unknown; for this reason, women
of child-bearing potential and men must agree to use adequate contraception (hormonal
or barrier method of birth control; abstinence) prior to study entry and for the
duration of study participation; 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 the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier

- Patients may not be receiving any other investigational agents

- Patients with known brain metastases may be enrolled if this site of disease has been
adequately treated, the patient does not require steroids, and the patient has been
stable for at least 3 months prior to enrollment

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to IL-12 or other agents used in study

- 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 because IL-12 is an agent with the
potential for teratogenic or abortifacient effects; because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with IL-12, breastfeeding should be discontinued if the mother is treated with
IL-12; these potential risks may also apply to other agents used in this study