Metastatic Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma, Unresectable Head and Neck Squamous Cell Carcinoma
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALCetuximab
Given IV
BIOLOGICALEdodekin alfa
Given SC
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Up to 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Induction of Systemic Plasma Levels of Interferon-gamma | Baseline up to day 50 | Explores graphically how changes in this marker differ between those with versus without an objective response to therapy as well as other potential factors. |
| Number of Confirmed Clinical Responses (Phase I) | Up to 6 months | 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. |
| Overall Survival (Phase II) | From the date of registration to date of death, assessed up to 1 year | The Kaplan-Meier method will be used to estimate overall survival distribution. |
| Proportion of Patients Who Are Progression-free (Phase I) | 6 months | 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 to Disease Progression (Phase II) | From date of registration to date of progression, assessed up to 1 year | The Kaplan-Meier method will be used to estimate time to progression distributions. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORWilliam E Carson
Ohio State University Comprehensive Cancer Center
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 (Phase 1) Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 (Dose Escalation) on days 2 and 5 of the 2 week cycle, beginning with cycle 2. | 6 |
| Arm II (Phase II) Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 at the MTD on days 2 and 5 of the 2 week cycle beginning with cycle 2. No IL-12 is given in the first cycle. IL-12 dosing will begin in cycle 2. The IL-12 dose is 0.3 mcg/kg. | 17 |
| Total | 23 |
Baseline characteristics
| Characteristic | Arm 1 (Phase 1) | Total | Arm II (Phase II) |
|---|---|---|---|
| Age, Continuous | 56.5 years | 61 years | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 22 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 19 Participants | 14 Participants |
| Region of Enrollment United States | 6 Participants | 23 Participants | 17 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 5 Participants | 22 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| other Total, other adverse events | 6 / 6 | 17 / 17 |
| serious Total, serious adverse events | 5 / 6 | 9 / 17 |
Outcome results
Primary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 (Phase I) | 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) | 2 Dose limiting toxicities |
| Arm II (Phase II) | 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) | 0 Dose limiting toxicities |
Primary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 (Phase I) | 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) | 0 proportion of patients |
Secondary
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
Population: Unable to compare the plasma levels of interferon-gamma between those with versus without an objective response to therapy due to no objective response seen for Phase I or Phase II patients.
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 (Phase I) | Number of Confirmed Clinical Responses (Phase I) | 0 Participants |
Secondary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm II (Phase II) | Overall Survival (Phase II) | 10.6 months |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 (Phase I) | Proportion of Patients Who Are Progression-free (Phase I) | .17 proportion of patients |
Secondary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm II (Phase II) | Time to Disease Progression (Phase II) | 4.6 months |