Know Cancer

forgot password

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of ARQ 197 Plus Erlotinib Versus Placebo Plus Erlotinib in Previously Treated Subjects With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer (NSCLC)

Phase 3
18 Years
Open (Enrolling)
Non Squamous, Non-small-cell Lung Cancer

Thank you

Trial Information

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of ARQ 197 Plus Erlotinib Versus Placebo Plus Erlotinib in Previously Treated Subjects With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer (NSCLC)

Inclusion Criteria:

- Histologically or cytologically confirmed surgically unresectable locally advanced or
metastatic (stage IIIB/IV) non-squamous non-small-cell lung cancer.

- Measurable disease and documented disease progression following last prior therapy
according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, Version

- Have received one or two prior lines of systemic anti-cancer therapy therapy for
advanced or metastatic disease, one of which must be a platinum-doublet therapy.
Patients who received only adjuvant treatment will be eligible only if disease
progression occurred <6 months after completion of adjuvant therapy. Prior
maintenance therapy is allowed and will be considered as the same line of therapy
when continued without discontinuation after initiation of a treatment regimen.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Resolution of any toxic effects of prior therapy (including radiotherapy) according
to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
(CTCAE), Version 4.0, Grade ≤1 (with the exception of alopecia and ≤grade 2
neuropathy). Subject must have recovered from significant surgery-related

- Demonstrate adequate bone marrow, liver, and renal functions, defined as:

- ALT, AST, and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN) in subjects
with no liver metastasis and ≤5.0 x ULN in subjects with liver metastasis.

- Total bilirubin ≤ 1.5 × ULN (≤ 4 × ULN total and ≤1.5 × ULN direct bilirubin is
acceptable for subjects with Gilbert's syndrome).

- ANC ≥1.5 × 10^9/L.

- Platelet count ≥100 × 10^9/L.

- Hemoglobin ≥9.0 g/dL (transfusion and/or growth factor support allowed).

- Serum creatinine ≤1.5 × ULN or creatinine clearance ≥ 60 mL/min.

- Archival and/or fresh biopsy tissue sample must be available for biomarker
determination. The status of the following biomarkers will be collected in this
study: EGFR and KRAS mutation status prior to randomization, and MET status post

- If of child-bearing/reproductive potential (female or male), must agree to use
double-barrier contraceptive measures, oral contraception, or avoidance of
intercourse during the study and for 90 days after last investigational drug dose

- If female and of childbearing potential, must have a negative result of a pregnancy
test (serum or urine) within 72 hours prior to initiating study treatment.

- Must have signed and dated an approved Informed Consent Form (Including HIPAA
authorization, if applicable) before performance of any study-specific procedures or
tests. Subjects must be fully informed about their illness and the investigational
nature of the study protocol (including forseeable risks and possible side effects)

Exclusion Criteria:

- Prior therapy with an EGFR inhibitor and/or ARQ 197 (or other known c-MET inhibitor).

- Receipt of any systemic anti-tumor treatment for NSCLC within 3 weeks prior to

- Receipt of palliative radiotherapy within 2 weeks or radiotherapy for curative intent
of target lesions within 3 weeks prior to randomization. Lesions subjected to
radiotherapy within 3 weeks prior to randomization may not be used as target lesions.

- Major surgical procedure within 3 weeks prior to randomization.

- History of cardiac disease:

Congestive heart failure defined as Class II to IV per New York Heart Association
classification; active coronary artery disease; previously diagnosed symptomatic
bradycardia (subjects with asymptomatic bradycardia and heart rate above 50 bpm are
allowed) or other cardiac arrhythmia defined as ≥Grade 2 according to NCI CTCAE, version
4.0, or uncontrolled hypertension; myocardial infarction that occurred within 6 months
prior to study entry (myocardial infarction that occurred > 6 months prior to study entry
is permitted).

- Clinically unstable central nervous system (CNS) metastasis (to be enrolled in the
study, subjects must have confirmation of stable disease by MRI or computed
tomography (CT) scan within 4 weeks of randomization and have CNS metastases well
controlled by steroids, anti-epileptics or other symptom-relieving medications).

- Need to breastfeed a child during or within 12 weeks of completing the study.

- Significant gastrointestinal disorder that, in the opinion of the investigator, could
interfere with absorption of ARQ 197 and/or erlotinib (eg, Crohn's disease, small or
large bowel resection, malabsorption syndrome).

- Inability or unwillingness to swallow the complete doses of ARQ 197 or erlotinib.

- Any known contraindication to treatment with, including hypersensitivity to, ARQ 197
or erlotinib.

- History of malignancy other than NSCLC within the 5 years prior to randomization,
with the exceptions of adequately treated intraepithelial carcinoma of the cervix
uteri; prostate carcinoma with a prostate-specific antigen value <0.2 ng/mL; or basal
or squamous-cell carcinoma of the skin.

- Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or
hepatitis C virus (HCV).

- Any other significant co-morbid condition that, in opinion of the investigator, would
impair study participation or cooperation.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

Overall survival of participants

Outcome Description:

The overall survival (OS) will be the primary efficacy endpoint for this study. OS is defined as the time from the date of randomization to the date of death from any cause. If there is no death reported for a subject before the cut-off date for OS analysis, OS will be censored at the last contact date at which the subject is known to be alive.

Outcome Time Frame:

Date of randomization to ≤ 30 months

Safety Issue:



United States: Food and Drug Administration

Study ID:

ARQ 197-A-U302



Start Date:

November 2010

Completion Date:

July 2013

Related Keywords:

  • Non Squamous, Non-small-cell Lung Cancer
  • Non squamous, non-small-cell lung cancer
  • Epidermal growth factor receptor, wild type
  • c-Met inhibitor
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Hinsdale, Illinois  60521
Alexandria, Minnesota  56308
Albany, Georgia  31701
Phoenix, Arizona  85012
Fountain Valley, California  92708
Miami, Florida  33176
Columbia, Missouri  65203
Albany, New York  12208
Cleveland, Ohio  44195
Philadelphia, Pennsylvania  19104
Nashville, Tennessee  37203-1632
Austin, Texas  78705
Seattle, Washington  98195
Louisville, Kentucky  40207
McLean, Virginia  22101
Omaha, Nebraska  68114
Hackensack, New Jersey  07601
Albuquerque, New Mexico  87131-5636
Denver, Colorado  
Baltimore, Maryland  21287
Boston, Massachusetts  
Eugene, Oregon  
Wilmington, Delaware  
Indianapolis, Indiana  
Charleston, South Carolina  
Las Vegas, Nevada  89109
Salt Lake City, Utah  84112