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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
ArQule
ClinicalTrials.gov Identifier:
NCT01395758
First received: July 1, 2011
Last updated: October 18, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Metastatic Non-Small Cell Lung Cancer
Drug: ARQ 197 plus erlotinib
Drug: Pemetrexed, docetaxel or gemcitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by ArQule:

Primary Outcome Measures:
  • The primary objective of this study is to evaluate median progression-free survival (PFS) among subjects with KRAS mutation positive NSCLC (ITT population) treated with erlotinib plus ARQ 197 compared to single agent chemotherapy. [ Time Frame: Date of randomization until disease progression per RECIST (Version 1.1) or death from any cause, whichever came first, assessed up to 24 months. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate median overall survival (OS) among all eligible subjects (ITT population) treated with erlotinib plus ARQ 197 compared to chemotherapy. [ Time Frame: Date of randomization to the date of death from any cause, assessed up to 24 months ] [ Designated as safety issue: No ]
  • To determine the objective response rate (ORR) among all eligible subjects (ITT population) treated with erlotinib plus ARQ 197 compared to chemotherapy. [ Time Frame: Date of randomization to the date of death from any cause or to the date that the subject discontinues from the study, assessed up to 24 months ] [ Designated as safety issue: No ]
  • To determine the objective response rate (ORR) among subjects randomly assigned to chemotherapy who cross over following disease progression to receive erlotinib plus ARQ 197 and who are evaluable for a post-progression scan on crossover therapy. [ Time Frame: Date of randomization to the date of death from any cause or to the date that the subject discontinues from the study, assessed up to 24 months. ] [ Designated as safety issue: No ]
  • To further characterize the safety (adverse events) of ARQ 197 in combination with erlotinib in subjects with KRAS mutation positive NSCLC. [ Time Frame: Every three weeks throughout the study period and up to 30 days after the last dose of study medication, assessed up to 24 months. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 98
Study Start Date: July 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tivantinib (ARQ 197) plus erlotinib arm

Eligible subjects will be randomly assigned to receive erlotinib plus tivantinib (ARQ 197).

Treatment will be open-label and continue until progression of disease, unacceptable toxicity, or another discontinuation criterion is met.

Drug: ARQ 197 plus erlotinib
Eligible subjects will be randomly assigned to receive erlotinib plus ARQ 197.
Other Name: Tivantinib
Active Comparator: Chemotherapy arm
A single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) administered according to approved labeling
Drug: Pemetrexed, docetaxel or gemcitabine
A single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) administered according to approved labeling.

Detailed Description:

This is a randomized, open-label Phase 2 study designed to compare treatment with erlotinib plus tivantinib (ARQ 197) versus single agent chemotherapy in subjects with previously treated KRAS mutation positive NSCLC. Eligible subjects are randomly assigned to receive erlotinib plus tivantinib or one of three (based on Investigator's decision) single-agent chemotherapy agents including pemetrexed, docetaxel, or gemcitabine.

  Eligibility

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

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 LCMC guidelines; see www.golcmc.com)
  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 EGFR
  2. Previous receipt of any c-MET inhibitor 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 administration
  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 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 CNS metastases well controlled by steroids, anti-epileptics or other symptom-relieving medications)
  14. Known EGFR-mutation positive status
  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: NCT01395758

Locations
United States, California
Stanford, California, United States, 94305
United States, District of Columbia
Washington, District of Columbia, United States, 20057
United States, Florida
Weston, Florida, United States, 33331
United States, Georgia
Atlanta, Georgia, United States, 30341
United States, Illinois
Chicago, Illinois, United States, 60611
United States, Kansas
Kansas City, Kansas, United States, 66160
United States, Maryland
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Boston, Massachusetts, United States, 02114
Burlington, Massachusetts, United States, 01805
United States, New York
New York, New York, United States, 10016
United States, Pennsylvania
Pittsburg, Pennsylvania, United States, 15232
United States, South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
Dallas, Texas, United States, 75390
Sponsors and Collaborators
ArQule
  More Information

No publications provided

Responsible Party: ArQule
ClinicalTrials.gov Identifier: NCT01395758     History of Changes
Other Study ID Numbers: ARQ 197-218
Study First Received: July 1, 2011
Last Updated: October 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by ArQule:
KRAS mutation
metastatic NSCLC

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Pemetrexed
Erlotinib
Docetaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on August 21, 2014