This phase I/II trial studies the side effects and best dose of recombinant interleukin-12 when given together with cetuximab and to see how well they work in treating patients with squamous cell carcinoma of the head and neck that has come back, spread to another place in the body, or cannot be removed by surgery. Recombinant interleukin-12 may stimulate the white blood cells to kill tumor cells. Immunotherapy with monoclonal antibodies, such as cetuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread Giving recombinant interleukin-12 together with cetuximab may kill more tumor cells.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
23
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Number of Dose-limiting Toxicity Incidents to Determine the Maximum Tolerated Dose of IL-12, Evaluated Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase I)
Time frame: 14 days
Proportion of Patients Who Have Any Response to Treatment (Complete Response or Partial Response), Determined According to Response Evaluation Criteria in Solid Tumors (Phase II)
The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Up to 6 months
Induction of Systemic Plasma Levels of Interferon-gamma
Explores graphically how changes in this marker differ between those with versus without an objective response to therapy as well as other potential factors.
Time frame: Baseline up to day 50
Number of Confirmed Clinical Responses (Phase I)
Summarized by simple descriptive summary statistics. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Up to 6 months
Overall Survival (Phase II)
The Kaplan-Meier method will be used to estimate overall survival distribution.
Time frame: From the date of registration to date of death, assessed up to 1 year
Proportion of Patients Who Are Progression-free (Phase I)
Summarized by simple descriptive summary statistics. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 6 months
Time to Disease Progression (Phase II)
The Kaplan-Meier method will be used to estimate time to progression distributions.
Time frame: From date of registration to date of progression, assessed up to 1 year
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