Cetuximab With or Without Tivantinib in Treating Patients With Head and Neck Cancer That Is Recurrent, Metastatic, or Cannot Be Removed By Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01696955
First received: September 28, 2012
Last updated: July 28, 2014
Last verified: May 2014
  Purpose

This randomized phase II trial studies how well cetuximab with or without tivantinib works in treating patients with head and neck cancer that is recurrent, metastatic, or cannot be removed by surgery. Monoclonal antibodies, such as cetuximab, can interfere with tumor growth by blocking the ability of tumor cells to grow and spread. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cetuximab is more effective with or without tivantinib in treating patients with head and neck cancer.


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
Drug: tivantinib
Biological: cetuximab
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of ARQ 197 (Tivantinib)/Cetuximab Versus Cetuximab in Patients With Recurrent/Metastatic Head and Neck Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response rate assessed according to RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Response rates in the two arms will be compared using a continuity-corrected chi square test. A sample size of n=38 patients per arm will provide 80% power to detect a difference of 12% vs 35% between the cetuximab and combination treatment arms, using a one-sided test at the alpha = 0.10 significance level.


Secondary Outcome Measures:
  • Change in tumor burden, measured using the sum of longest diameters of target lesion [ Time Frame: Baseline to 8 weeks ] [ Designated as safety issue: No ]
    Early change in tumor burden will be compared between groups using two-sample t-tests. Waterfall plots will be constructed for graphical comparison.

  • PFS [ Time Frame: From start of treatment to time of progression or death of any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    Kaplan-Meier curves will be generated for PFS and the treatment arms compared via log rank tests.

  • OS [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Kaplan-Meier curves will be generated for OS and the treatment arms compared via log rank tests.

  • Change in c-MET expression [ Time Frame: Baseline to 8 weeks ] [ Designated as safety issue: No ]
    Change in tumor burden, PFS, and OS in subgroup of patients with high c-MET expression and/or high c-MET copy number. Logistic and Cox proportional hazards regression models to examine the change in tumor burden, PFS, and OS in subgroup of patients with high c-MET expression and/or high c-MET copy number.

  • Change in c-MET copy number [ Time Frame: Baseline to 8 weeks ] [ Designated as safety issue: No ]
    Change in tumor burden, PFS, and OS in subgroup of patients with high c-MET expression and/or high c-MET copy number. Logistic and Cox proportional hazards regression models to examine the change in tumor burden, PFS, and OS in subgroup of patients with high c-MET expression and/or high c-MET copy number.

  • Activity of single-agent tivantinib after failure of cetuximab [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 76
Study Start Date: August 2012
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (cetuximab and tivantinib)
Patients receive cetuximab IV over 60-120 minutes on days 1 and 15 and tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: tivantinib
Given PO
Other Name: ARQ 197
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (cetuximab)
Patients receive cetuximab IV over 60-120 minutes on days 1 and 15. Patients who fail cetuximab as a single agent may receive single agent tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Response rate. We will compare the cetuximab/ARQ 197 (tivantinib) combination with cetuximab single agent activity.

SECONDARY OBJECTIVES:

I. Continuous tumor shrinkage. II. Progression-free survival (PFS). III. Overall survival (OS). IV. Endpoints I), II), and III) above, as well as response rates, will be assessed and compared between treatment arms in the subgroup of patients with high mesenchymal epithelial transition factor (c-MET) expression, and/or high c-MET copy number.

V. Single agent activity for ARQ 197 (tivantinib) in patients who have failed cetuximab.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cetuximab intravenously (IV) over 60-120 minutes on days 1 and 15 and tivantinib orally (PO) twice daily (BID) on days 1-28.

ARM II: Patients receive cetuximab IV over 60-120 minutes on days 1 and 15. Patients who fail cetuximab as a single agent may receive single agent tivantinib PO BID on days 1-28.

In both arms, courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically/cytologically confirmed diagnosis of squamous cell carcinoma of head and neck origin not amenable to curative intent therapy; both human papillomavirus (HPV) positive (+) and HPV negative (-) are eligible, but status has to be known prior to randomization (although not required for consenting); any type of tissue based HPV assessment is acceptable (e.g. p16 immunohistochemistry [IHC] or HPV in situ hybridization [ISH]); if local HPV testing is not available slides can be sent to the University of Chicago for HPV testing; please note that p16 IHC is generally only considered to be accurate for oropharyngeal tumors
  • Presence of measurable lesions (as per Response Evaluation Criteria in Solid Tumors [RECIST]1.1); generally a >= 10 mm tumor lesion (in the longest diameter by computed tomography [CT] scan) or a lymph node >= 15 mm (short axis) is considered measurable disease when evaluated by CT scan (with a slice thickness no greater than 5 mm)
  • Availability of tissue (10 tumor containing formalin-fixed, paraffin-embedded [FFPE] slides/sections)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1
  • Patients who have received cetuximab or another inhibitor of epidermal growth factor receptor (EGFR) in the curative intent treatment setting (e.g. with radiation or during induction chemotherapy [prior to definitive, curative intent therapy]) are eligible for the study
  • Life expectancy of greater than 8 weeks
  • Hemoglobin >= 9.0 g/dL
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 X institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Serum creatinine =< 1.5 X institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Patients must be able to swallow ARQ 197 (tivantinib) by mouth, unless adequate data about administration by gastrostomy (G)-tube becomes available; tablets may be crushed, but must be taken orally
  • Human immunodeficiency virus (HIV)-positive patients with normal immune function (cluster of differentiation [CD]4 count > 200) are eligible if there are no drug interactions with ARQ 197 (tivantinib) or cetuximab
  • 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 she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ARQ 197 (tivantinib) administration
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 2 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 2 weeks earlier
  • Nasopharyngeal tumors that show lymphoepithelioma histology
  • Patients who have received more than 2 prior cytotoxic treatments in the palliative treatment setting are ineligible
  • Patients who have received treatment with an EGFR or MET inhibitor in the palliative treatment setting are ineligible
  • Patients with known, active brain metastases should be excluded from this clinical trial; patients with treated brain metastases stable for >= 12 weeks are eligible; use of corticosteroid (for patients with brain metastasis and other indications for corticosteroid use) is acceptable on a low maintenance or tapering dose schedule
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ARQ 197 (tivantinib) or cetuximab
  • Concurrent life-threatening diseases: patients with diseases which with reasonable certainty do not limit life expectancy to 12 months or less are eligible; assessment of such concurrent illnesses should be by the principal investigator
  • 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 ARQ 197 (tivantinib)
  • Concurrent use of warfarin (therapeutic use) is allowed, but requires close monitoring of prothrombin time (PT)/international normalized ratio (INR)
  • History of congestive heart failure defined as class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD), clinically significant bradycardia or other uncontrolled, cardiac arrhythmia defined as >= grade 3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, or uncontrolled hypertension; myocardial infarction occurring within 6 months prior to study entry (myocardial infarction occurring > 6 months prior to study entry is permitted)
  • Patients may not be receiving any other investigational agents
  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: NCT01696955

Locations
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Kelly K. Curtis    480-301-8296    Curtis.kelly1@mayo.edu   
Principal Investigator: Kelly K. Curtis         
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Dean W. Lim    626-256-4673    Dlim@coh.org   
Principal Investigator: Dean W. Lim         
University of Southern California/Norris Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Barbara J. Gitlitz    323-865-3959    gitlitz@usc.edu   
Principal Investigator: Barbara J. Gitlitz         
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Barbara J. Gitlitz    323-865-3959    gitlitz@usc.edu   
Principal Investigator: Barbara J. Gitlitz         
City of Hope Medical Group Inc Recruiting
Pasadena, California, United States, 91105
Contact: Stephen C. Koehler    626-396-2900    Skoehler@cohmg.com   
Principal Investigator: Stephen C. Koehler         
University of California at Davis Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: David R. Gandara    916-734-3771    david.gandara@ucdmc.ucdavis.edu   
Principal Investigator: David R. Gandara         
City of Hope South Pasadena Recruiting
South Pasadena, California, United States, 91030
Contact: Stephen C. Koehler    626-396-2900    Skoehler@cohmg.com   
Principal Investigator: Stephen C. Koehler         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Tanguy Y. Seiwert    773-702-2452    tseiwert@medicine.bsd.uchicago.edu   
Principal Investigator: Tanguy Y. Seiwert         
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Mark Agulnik    312-695-0990    m-agulnik@northwestern.edu   
Principal Investigator: Mark Agulnik         
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Mark Agulnik    312-695-0990    m-agulnik@northwestern.edu   
Principal Investigator: Mark Agulnik         
Decatur Memorial Hospital Recruiting
Decatur, Illinois, United States, 62526
Contact: James L. Wade    217-876-6600    JLWADE3@sbcglobal.net   
Principal Investigator: James L. Wade         
NorthShore University HealthSystem-Evanston Hospital Recruiting
Evanston, Illinois, United States, 60201
Contact: Bruce E. Brockstein    847-570-2515    bbrockstein@northshore.org   
Principal Investigator: Bruce E. Brockstein         
Ingalls Memorial Hospital Recruiting
Harvey, Illinois, United States, 60426
Contact: Mark F. Kozloff    708-339-4800    mfkozloff@aol.com   
Principal Investigator: Mark F. Kozloff         
Illinois CancerCare-Peoria Recruiting
Peoria, Illinois, United States, 61615
Contact: Sachdev P. Thomas    309-243-3605    sthomas@illinoiscancercare.com   
Principal Investigator: Sachdev P. Thomas         
Southern Illinois University School of Medicine - Department of Surgery Recruiting
Springfield, Illinois, United States, 62702
Contact: Krishna A. Rao    217-545-7969    krao@siumed.edu   
Principal Investigator: Krishna A. Rao         
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc-Parkview Recruiting
Fort Wayne, Indiana, United States, 46845
Contact: Sreenivasa R. Nattam    260-484-8830    ledgar@fwmoh.com   
Principal Investigator: Sreenivasa R. Nattam         
Indiana University Medical Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Stephanie A. Wagner    317-962-9000    wagnerst@iupui.edu   
Principal Investigator: Stephanie A. Wagner         
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Mohammed M. Milhem    319-356-2324    mohammed-milhem@uiowa.edu   
Principal Investigator: Mohammed M. Milhem         
United States, Maryland
University of Maryland/Greenebaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Dan P. Zandberg    410-328-7904    dzandberg@umm.edu   
Principal Investigator: Dan P. Zandberg         
United States, Michigan
University of Michigan University Hospital Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Francis P. Worden    734-936-0453    fworden@umich.edu   
Principal Investigator: Francis P. Worden         
Wayne State University/Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Ammar Sukari    313-576-8778    sukaria@karmanos.org   
Principal Investigator: Ammar Sukari         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Katharine A. Price    507-284-2511    price.katherine@mayo.edu   
Principal Investigator: Katharine A. Price         
Metro-Minnesota CCOP Recruiting
Saint Louis Park, Minnesota, United States, 55416
Contact: Daniel M. Anderson    952-993-1517    Daniel.m.anderson@healthpartners.com   
Principal Investigator: Daniel M. Anderson         
United States, Missouri
Saint John's Mercy Medical Center Recruiting
Saint Louis, Missouri, United States, 63141
Contact: Bethany G. Sleckman    314-251-7057    slecbg@stlo.mercy.net   
Principal Investigator: Bethany G. Sleckman         
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Douglas R. Adkins    314-362-5654    dadkins@dom.wustl.edu   
Principal Investigator: Douglas R. Adkins         
United States, Pennsylvania
Penn State Milton S Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Contact: Chandra P. Belani    717-531-1078    cbelani@psu.edu   
Principal Investigator: Chandra P. Belani         
UPMC Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Julie E. Bauman    412-648-6589    baumanje@upmc.edu   
Principal Investigator: Julie E. Bauman         
Sponsors and Collaborators
Investigators
Principal Investigator: Tanguy Seiwert University of Chicago Phase 2 Consortium
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01696955     History of Changes
Other Study ID Numbers: NCI-2012-01640, NCI-2012-01640, 478834, 12-1359, 9165, N01CM00071, N01CM00038, P30CA014599, N01CM00099
Study First Received: September 28, 2012
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 15, 2014