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A Randomized Phase II Trial of ARQ 197 (Tivantinib)/Cetuximab Versus Cetuximab in Patients With Recurrent/Metastatic Head and Neck Cancer


Phase 2
18 Years
N/A
Open (Enrolling)
Both
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

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Trial Information

A Randomized Phase II Trial of ARQ 197 (Tivantinib)/Cetuximab Versus Cetuximab in Patients With Recurrent/Metastatic Head and Neck Cancer


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 c-MET expression
(anticipated to be ~84% of patients, and/or high c-MET copy number (anticipated >10% and
largely overlapping with MET IHC).

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 8 weeks.


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; any type of tissue based HPV assessment is acceptable (e.g.
p16 immunohistochemistry [IHC] or in situ hybridization [ISH]); if local HPV testing
is not available slides can be sent to the University of Chicago for HPV testing
using p16 IHC or comparable

- Presence of measurable lesions (Response Evaluation Criteria in Solid Tumors
[RECIST])

- Availability of tissue (>= 17 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 glutamic pyruvic 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

- Presence of measurable lesions by RECIST: patients must have measurable disease,
defined as at least one lesion that can be accurately measured in at least one
dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques
or as >= 10 mm with spiral computed tomography (CT) scan

- 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

- Patients must be able to swallow ARQ 197 (tivantinib) by mouth, unless adequate data
about administration by gastronomy tube (G-tube) becomes available

Exclusion Criteria:

- Patients who have ad 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

- Patients with tumors that progress within 3 months of definitive treatment (typically
chemoradiation or radiation) are ineligible

- 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 corticosteroids 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)

- ARQ 197 (tivantinib) is metabolized by cytochrome P450 2C19 (CYP2C19), and to a
lesser extent cytochrome P450 3A4 (CYP3A4); the metabolism and consequently overall
pharmacokinetics of ARQ 197 (tivantinib) could be altered by inhibitors and/or
inducers or other substrates of CYP2C19 and CYP3A4; while inhibitors/inducers of
these cytochrome P450 isoenzymes are not specifically excluded, investigators should
be aware that ARQ 197 (tivantinib) exposure may be altered by the concomitant
administration of these drugs

- History of congestive heart failure defined as class II to IV per New York Heart
Association (NYHA) classification; 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate (RECIST)

Outcome Description:

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.

Outcome Time Frame:

Up to 8 weeks after completion of study treatment

Safety Issue:

No

Principal Investigator

Tanguy Seiwert

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01640

NCT ID:

NCT01696955

Start Date:

August 2012

Completion Date:

Related Keywords:

  • 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
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms
  • Laryngeal Diseases
  • Tongue Neoplasms
  • Carcinoma, Verrucous
  • Neoplasms, Unknown Primary
  • Salivary Gland Neoplasms
  • Hypopharyngeal Neoplasms
  • Laryngeal Neoplasms
  • Paranasal Sinus Neoplasms
  • Oropharyngeal Neoplasms
  • Nasopharyngeal Neoplasms

Name

Location

Mayo ClinicRochester, Minnesota  55905
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Indiana University Cancer CenterIndianapolis, Indiana  46202-5265
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
Northwestern Memorial HospitalChicago, Illinois  60611
Ingalls Memorial HospitalHarvey, Illinois  60426
City of Hope Comprehensive Cancer CenterDuarte, California  91010
Mayo Clinic in ArizonaScottsdale, Arizona  85259-5404
Mayo Clinic in FloridaJacksonville, Florida  32224
Wayne State UniversityDetroit, Michigan  48202
USC Norris Comprehensive Cancer CenterLos Angeles, California  90089
UPMC Hillman Cancer CenterPittsburgh, Pennsylvania  15232
Metro-Minnesota CCOPSt. Louis Park, Minnesota  
UC Davis Comprehensive Cancer CenterSacramento, California  95817
Decatur Memorial HospitalDecatur, Illinois  62526
Penn State Milton S Hershey Medical CenterHershey, Pennsylvania  17033
Evanston CCOP-NorthShore University HealthSystemEvanston, Illinois  60201
Illinois CancerCare-PeoriaPeoria, Illinois  61615
Fort Wayne Medical Oncology and Hematology Inc - State BoulevardFort Wayne, Indiana  46845
Saint John's Mercy Medical CenterSaint Louis, Missouri  63141
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201
University of Colorado Cancer Center - Anschutz Cancer PavilionAurora, Colorado  80045
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins HospitalBaltimore, Maryland  21231
University of Wisconsin Cancer Center RiverviewWisconsin Rapids, Wisconsin  54494
Siteman Cancer Center at Washington UniversitySaint Louis, Missouri  63110
Southern Illinois University School of Medicine - Department of SurgerySpringfield, Illinois  62702