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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase I/II Trial of Cetuximab in Combination With Interleukin-12 Administered to Patients With Unresectable Primary or Recurrent Squamous Cell Carcinoma of the Head and Neck

Conditions
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Metastatic Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma, Unresectable Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Biological: Cetuximab
* Biological: Edodekin alfa
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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: Treatment (cetuximab and recombinant interleukin-12)<br>Patients receive cetuximab IV over 1-2 hours on day 1 and recombinant interleukin-12 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. | Biological: Cetuximab<br>* Given IV<br>* Other names: IMC-C225;Biological: Edodekin alfa<br>* Given SC<br>* Other names: Ro 24-7472;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) |  | 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. | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | Up to 6 months | 
| Overall Survival (Phase II) | The Kaplan-Meier method will be used to estimate overall survival distribution. | 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. | 6 months | 
| Time to Disease Progression (Phase II) | The Kaplan-Meier method will be used to estimate time to progression distributions. | From date of registration to date of progression, assessed up to 1 year |