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
  Purpose

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.


Condition Intervention Phase
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
Biological: recombinant interleukin-12
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

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) [ 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 47
Study Start Date: October 2011
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 (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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01468896

Locations
United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University Recruiting
Washington, District of Columbia, United States, 20057
Contact: Stephen V. Liu    202-444-7935    stephen.v.liu@gunet.georgetown.edu   
Principal Investigator: Stephen V. Liu         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Yujie Zhao    716-845-8568    yujie.zhao@roswellpark.org   
Principal Investigator: Yujie Zhao         
United States, Ohio
Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Michael K. Gibson    216-844-5586    Michael.Gibson@UHhospitals.org   
Principal Investigator: Michael K. Gibson         
Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: William E. Carson    614-293-6306    william.carson@osumc.edu   
Principal Investigator: William E. Carson         
Sponsors and Collaborators
Investigators
Principal Investigator: William Carson Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01468896     History of Changes
Other Study ID Numbers: NCI-2011-03631, NCI-2011-03631, 11010, CDR0000715306, OSU 11010, 8860, U01CA076576, P30CA016058, UM1CA186712
Study First Received: November 8, 2011
Last Updated: September 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Laryngeal Diseases
Laryngeal Neoplasms
Oropharyngeal Neoplasms
Carcinoma, Verrucous
Nasopharyngeal Neoplasms
Paranasal Sinus Neoplasms
Salivary Gland Neoplasms
Neoplasms, Unknown Primary
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Respiratory Tract Neoplasms
Pharyngeal Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Nasopharyngeal Diseases
Nose Neoplasms
Nose Diseases
Paranasal Sinus Diseases
Mouth Neoplasms
Mouth Diseases
Salivary Gland Diseases

ClinicalTrials.gov processed this record on October 19, 2014