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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 Purpose

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

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cetuximab
Edodekin alfa
Laboratory Biomarker Analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Head and Neck Squamous Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • MedStar Georgetown University Hospital
  • Ohio State University Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (cetuximab and recombinant interleukin-12)

Arm Description

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.

Outcomes

Primary Outcome Measures

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)
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.

Secondary Outcome Measures

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.
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.
Overall Survival (Phase II)
The Kaplan-Meier method will be used to estimate overall survival distribution.
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 to Disease Progression (Phase II)
The Kaplan-Meier method will be used to estimate time to progression distributions.

Full Information

First Posted
November 8, 2011
Last Updated
September 12, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01468896
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 26, 2011 (Actual)
Primary Completion Date
September 29, 2015 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma, Unresectable Head and Neck Squamous Cell Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (cetuximab and recombinant interleukin-12)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
C225, Cetuximab Biosimilar CDP-1, Cetuximab Biosimilar CMAB009, Cetuximab Biosimilar KL 140, Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux, IMC-C225
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Edodekin alfa
Other Intervention Name(s)
Cytotoxic Lymphocyte Maturation Factor, IL-12, Interleukin 12, Interleukin-12, Natural Killer Cell Stimulatory Factor, NM-IL-12, Recombinant human interleukin-12 (IL-12) cytokine, Ro 24-7472
Intervention Description
Given SC
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
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
Title
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)
Description
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
Secondary Outcome Measure Information:
Title
Induction of Systemic Plasma Levels of Interferon-gamma
Description
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
Title
Number of Confirmed Clinical Responses (Phase I)
Description
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
Title
Overall Survival (Phase II)
Description
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
Title
Proportion of Patients Who Are Progression-free (Phase I)
Description
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
Title
Time to Disease Progression (Phase II)
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William E Carson
Organizational Affiliation
Ohio State University Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
MedStar Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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