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 August 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: September 23, 2014
Last verified: August 2014

November 8, 2011
September 23, 2014
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
  • Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
  • Recurrent Metastatic Squamous Neck Cancer With Occult Primary
  • Recurrent Salivary Gland Cancer
  • Recurrent Squamous Cell Carcinoma of the Hypopharynx
  • Recurrent Squamous Cell Carcinoma of the Larynx
  • Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Recurrent Squamous Cell Carcinoma of the Nasopharynx
  • Recurrent Squamous Cell Carcinoma of the Oropharynx
  • Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Recurrent Verrucous Carcinoma of the Larynx
  • Recurrent Verrucous Carcinoma of the Oral Cavity
  • Salivary Gland Squamous Cell Carcinoma
  • Stage III Salivary Gland Cancer
  • Stage III Squamous Cell Carcinoma of the Hypopharynx
  • Stage III Squamous Cell Carcinoma of the Larynx
  • Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage III Squamous Cell Carcinoma of the Nasopharynx
  • Stage III Squamous Cell Carcinoma of the Oropharynx
  • Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage III Verrucous Carcinoma of the Larynx
  • Stage III Verrucous Carcinoma of the Oral Cavity
  • Stage IV Squamous Cell Carcinoma of the Hypopharynx
  • Stage IV Squamous Cell Carcinoma of the Nasopharynx
  • Stage IVA Salivary Gland Cancer
  • Stage IVA Squamous Cell Carcinoma of the Larynx
  • Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVA Squamous Cell Carcinoma of the Oropharynx
  • Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVA Verrucous Carcinoma of the Larynx
  • Stage IVA Verrucous Carcinoma of the Oral Cavity
  • Stage IVB Salivary Gland Cancer
  • Stage IVB Squamous Cell Carcinoma of the Larynx
  • Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVB Squamous Cell Carcinoma of the Oropharynx
  • Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVB Verrucous Carcinoma of the Larynx
  • Stage IVB Verrucous Carcinoma of the Oral Cavity
  • Stage IVC Salivary Gland Cancer
  • Stage IVC Squamous Cell Carcinoma of the Larynx
  • Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IVC Squamous Cell Carcinoma of the Oropharynx
  • Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IVC Verrucous Carcinoma of the Larynx
  • Stage IVC Verrucous Carcinoma of the Oral Cavity
  • Tongue Cancer
  • Untreated Metastatic Squamous Neck Cancer With Occult Primary
  • Biological: cetuximab
    Given IV
    Other Names:
    • C225
    • C225 monoclonal antibody
    • IMC-C225
    • MOAB C225
    • monoclonal antibody C225
  • Biological: recombinant interleukin-12
    Given SC
    Other Names:
    • cytotoxic lymphocyte maturation factor
    • IL-12
    • interleukin-12
    • natural killer cell stimulatory factor
    • Ro 24-7472
  • 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 (PS) =< 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, U01CA076576, P30CA016058, UM1CA186712
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: William Carson Ohio State University
National Cancer Institute (NCI)
August 2014

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