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

NCT01696955 | Completed Phase 2 Results

• 8 other identifiers: NCI-2012-0164012-13594788349165N01CM00038N01CM00071N01CM00099P30CA014599
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 24

Brief Summary

This randomized phase II trial studies how well cetuximab with or without tivantinib works in treating patients with head and neck cancer that has come back (recurrent), has spread to other places in the body (metastatic), or cannot be removed by surgery. Monoclonal antibodies, such as cetuximab, may interfere with 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.

Conditions

Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or 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

  Up to 1 year

Secondary Outcomes (6)

• c-MET Copy Number

  Baseline to 8 weeks

• c-MET Expression

  Baseline to 8 weeks

• Change in Tumor Burden

  Baseline to 8 weeks

• Overall Survival

  Up to 5 years

• Progression-free Survival

  Up to 3 years

Other Outcomes (2)

• Number of Participants With Adverse Events While on Single-agent Tivantinib After Failure of Cetuximab

  Up to 3 years

• Number of Patients With Serious Adverse Events While on Single-agent Tivantinib After Failure of Cetuximab

  3 years

Study Arms (2)

Arm I (cetuximab and tivantinib)

EXPERIMENTAL

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.

Biological: Cetuximab; Other: Laboratory Biomarker Analysis; Drug: Tivantinib

Arm II (cetuximab)

EXPERIMENTAL

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; Other: Laboratory Biomarker Analysis

Interventions

Cetuximab BIOLOGICAL

Given IV

Arm I (cetuximab and tivantinib); Arm II (cetuximab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (cetuximab and tivantinib); Arm II (cetuximab)

Tivantinib DRUG

Given PO

Arm I (cetuximab and tivantinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (24)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

Location

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, 46845, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cetuximab; ARQ 197

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Theodore Karrison
• Organization: University of Chicago

tkarrison@health.bsd.uchicago.edu

773-702-9326

Study Officials

• Tanguy Seiwert

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2012
• First Posted: October 2, 2012
• Study Start: August 20, 2012
• Primary Completion: May 5, 2017
• Study Completion: May 5, 2017
• Last Updated: December 19, 2018
• Results First Posted: December 19, 2018

Record last verified: 2018-11

Locations

US (24)