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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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01468896
First received: November 8, 2011
Last updated: February 18, 2015
Last verified: December 2014

November 8, 2011
February 18, 2015
October 2011
December 2015   (final data collection date for primary outcome measure)
  • 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 ] [ Designated as safety issue: Yes ]
  • 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) [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    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.
  • Number of dose-limiting toxicity incidents (phase I) [ Designated as safety issue: Yes ]
  • Proportion of patients who have any response to treatment (phase II) [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01468896 on ClinicalTrials.gov Archive Site
  • Proportion of patients who are progression-free (phase I) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Summarized by simple descriptive summary statistics.
  • Number of confirmed clinical responses (phase I) [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    Summarized by simple descriptive summary statistics.
  • Overall survival (phase II) [ Time Frame: From the date of registration to date of death, assessed up to 1 year ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used to estimate overall survival distribution.
  • Time to disease progression (phase II) [ Time Frame: From date of registration to date of progression, assessed up to 1 year ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used to estimate time to progression distributions.
  • Induction of systemic plasma levels of interferon-gamma [ Time Frame: Baseline up to day 50 ] [ Designated as safety issue: No ]
    Explores graphically how changes in this marker differ between those with versus without an objective response to therapy as well as other potential factors.
  • Proportion of patients who are progression-free at 6 months (phase I) [ Designated as safety issue: No ]
  • Number of confirmed clinical responses (phase I) [ Designated as safety issue: No ]
  • Overall survival (phase II) [ Designated as safety issue: No ]
  • Time to disease progression (phase II) [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
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

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. Monoclonal antibodies, such as cetuximab, 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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Hypopharyngeal Squamous Cell Carcinoma
  • Recurrent Laryngeal Squamous Cell Carcinoma
  • Recurrent Laryngeal Verrucous Carcinoma
  • Recurrent Lip and Oral Cavity Squamous Cell Carcinoma
  • Recurrent Metastatic Squamous Cell Carcinoma to the Neck With Occult Primary
  • Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma
  • Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma
  • Recurrent Oral Cavity Verrucous Carcinoma
  • Recurrent Oropharyngeal Squamous Cell Carcinoma
  • Recurrent Salivary Gland Carcinoma
  • Salivary Gland Squamous Cell Carcinoma
  • Squamous Cell Carcinoma Metastatic to the Neck With Occult Primary
  • Stage III Hypopharyngeal Squamous Cell Carcinoma
  • Stage III Laryngeal Squamous Cell Carcinoma
  • Stage III Laryngeal Verrucous Carcinoma
  • Stage III Lip and Oral Cavity Squamous Cell Carcinoma
  • Stage III Major Salivary Gland Carcinoma
  • Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma
  • Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma
  • Stage III Oral Cavity Verrucous Carcinoma
  • Stage III Oropharyngeal Squamous Cell Carcinoma
  • Stage IV Hypopharyngeal Squamous Cell Carcinoma
  • Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma
  • Stage IVA Laryngeal Squamous Cell Carcinoma
  • Stage IVA Laryngeal Verrucous Carcinoma
  • Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma
  • Stage IVA Major Salivary Gland Carcinoma
  • Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma
  • Stage IVA Oral Cavity Verrucous Carcinoma
  • Stage IVA Oropharyngeal Squamous Cell Carcinoma
  • Stage IVB Laryngeal Squamous Cell Carcinoma
  • Stage IVB Laryngeal Verrucous Carcinoma
  • Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma
  • Stage IVB Major Salivary Gland Carcinoma
  • Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma
  • Stage IVB Oral Cavity Verrucous Carcinoma
  • Stage IVB Oropharyngeal Squamous Cell Carcinoma
  • Stage IVC Laryngeal Squamous Cell Carcinoma
  • Stage IVC Laryngeal Verrucous Carcinoma
  • Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma
  • Stage IVC Major Salivary Gland Carcinoma
  • Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma
  • Stage IVC Oral Cavity Verrucous Carcinoma
  • Stage IVC Oropharyngeal Squamous Cell Carcinoma
  • Tongue Carcinoma
  • Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary
  • Biological: Cetuximab
    Given IV
    Other Names:
    • Chimeric MoAb C225
    • Erbitux
    • IMC-C225
  • Biological: Recombinant Interleukin-12
    Given SC
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Experimental: Treatment (cetuximab and recombinant interleukin-12)
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.
Interventions:
  • Biological: Cetuximab
  • Biological: Recombinant Interleukin-12
  • Other: Laboratory Biomarker Analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
47
Not Provided
December 2015   (final data collection date for primary outcome measure)

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
  • 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; 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
Both
18 Years and older
No
United States
 
NCT01468896
NCI-2011-03631, NCI-2011-03631, 11010, CDR0000715306, OSU 11010, 8860, P30CA016058, N01CM00070, U01CA076576, UM1CA186712
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: William Carson Ohio State University Comprehensive Cancer Center
National Cancer Institute (NCI)
December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP