Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Not Recruiting

Trial ID: NCT01395758


The purpose of this study is to evaluate progression-free survival among subjects with KRAS mutation positive Non-Small Cell Lung Cancer (NSCLC) treated with erlotinib plus tivantinib (ARQ 197) compared to single agent chemotherapy.

Official Title

A Phase 2 Randomized Open-label Study of Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy in Previously Treated KRAS Mutation Positive Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Stanford Investigator(s)

Heather Wakelee
Heather Wakelee

Winston Chen and Phyllis Huang Professor

Joel Neal, MD, PhD
Joel Neal, MD, PhD

Associate Professor of Medicine (Oncology)

Kavitha Ramchandran
Kavitha Ramchandran

Clinical Professor, Medicine - Oncology

A. Dimitrios Colevas, MD
A. Dimitrios Colevas, MD

Professor of Medicine (Oncology) and, by courtesy, of Otolaryngology - Head & Neck Surgery (OHNS) and of Radiation Oncology (Radiation Therapy)


Inclusion Criteria:

   1. Provide signed and dated informed consent prior to study-specific screening procedures

   2. Male or female at least 18 years of age

   3. Histologically or cytologically confirmed inoperable locally advanced or metastatic
   (stage IVA/IVB) NSCLC

   4. Documented KRAS mutation positive status (per Lung Cancer Mutation Consortium [LCMC]
   guidelines; see

   5. At least one prior chemotherapy regimen for advanced NSCLC

   6. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
   criteria, Version 1.1

   7. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

   8. Male or female subjects of child-producing potential must agree to use double barrier
   contraception, oral contraceptives or avoidance of pregnancy measures during the study
   and for 90 days after the last day of treatment

   9. Females of childbearing potential must have a negative serum pregnancy test

10. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × upper limit of
   normal (ULN) or ≤ 5 × ULN with metastatic liver disease

11. Total bilirubin ≤ 1.5 × ULN

12. Serum creatinine ≤ 1.5 × ULN

13. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

14. Platelets ≥ 100 x 10^9/L

15. Hemoglobin ≥ 10 g/dL (transfusion is allowed at least 7 days prior to randomization)

16. Subjects must agree to allow testing for c-Met status if archival and/or fresh tissue
   biopsy samples are available.

Exclusion Criteria:

   1. Previous receipt of erlotinib or other epidermal growth factor receptor (EGFR)

   2. Previous receipt of any c-MET inhibitor (a receptor tyrosine kinase) or other
   c-MET-targeted therapy, including ARQ 197, MetMab, crizotinib

   3. Prior receipt of chemotherapy agent selected for administration in this study (e.g.,
   if subject was treated with gemcitabine, he is not eligible to receive gemcitabine in
   this study but eligible to receive pemetrexed or docetaxel).

   4. Inability or unwillingness to receive ARQ 197, erlotinib, docetaxel, gemcitabine,
   and/or pemetrexed including contraindications, hypersensitivity, or prior

   5. Receipt of any anti-tumor treatment for NSCLC within 3 weeks (2 weeks for
   radiotherapy) prior to randomization

   6. Pregnant or breastfeeding

   7. Significant gastrointestinal disorder that could, in the opinion of the Investigator,
   interfere with the absorption of ARQ 197 and/or erlotinib

   8. Any other significant co-morbid conditions that in the opinion of the Investigator
   would impair study participation or cooperation

   9. Other malignancies within the last three years, with the exception of adequately
   treated intraepithelial carcinoma of the cervix uteri, prostate carcinoma with a
   prostate-specific antigen (PSA) value < 0.2 ng/mL or basal or squamous cell carcinoma
   of the skin

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

11. Major surgical procedure within 4 weeks prior to randomization

12. 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 bradycardia or other cardiac arrhythmia defined as ≥ Grade 2 according to
   National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
   (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)

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

14. Known EGFR-mutation positive status


drug: ARQ 197 plus erlotinib

drug: Pemetrexed, docetaxel or gemcitabine

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cancer Clinical Trials Office

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