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Metastatic Non-Small Cell Lung CancerPhase 2NCT01395758

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

A Phase 2 study testing ARQ 197 plus erlotinib and Pemetrexed, docetaxel or gemcitabine in people with Metastatic Non-Small Cell Lung Cancer, run by ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Non-Small Cell Lung Cancer
What is being tested?
ARQ 197 plus erlotinib and Pemetrexed, docetaxel or gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
13 sitesUnited States
Study dates
Jul 2011to Aug 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provide signed and dated informed consent prior to study-specific screening procedures
  • Male or female at least 18 years of age
  • Histologically or cytologically confirmed inoperable locally advanced or metastatic (stage IVA/IVB) NSCLC
  • Documented KRAS mutation positive status (per Lung Cancer Mutation Consortium [LCMC] guidelines; see www.golcmc.com)
  • At least one prior chemotherapy regimen for advanced NSCLC
  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, Version 1.1
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  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • 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
  • Females of childbearing potential must have a negative serum pregnancy test
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 × ULN with metastatic liver disease
  • Total bilirubin ≤ 1.5 × ULN
  • Serum creatinine ≤ 1.5 × ULN
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
  • Platelets ≥ 100 x 10^9/L
  • Hemoglobin ≥ 10 g/dL (transfusion is allowed at least 7 days prior to randomization)
  • Subjects must agree to allow testing for c-Met status if archival and/or fresh tissue biopsy samples are available.

Who cannot join

  • Previous receipt of erlotinib or other epidermal growth factor receptor (EGFR) inhibitors
  • Previous receipt of any c-MET inhibitor (a receptor tyrosine kinase) or other c-MET-targeted therapy, including ARQ 197, MetMab, crizotinib
  • 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).
  • Inability or unwillingness to receive ARQ 197, erlotinib, docetaxel, gemcitabine, and/or pemetrexed including contraindications, hypersensitivity, or prior administration
  • Receipt of any anti-tumor treatment for NSCLC within 3 weeks (2 weeks for radiotherapy) prior to randomization
  • Pregnant or breastfeeding
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  • Significant gastrointestinal disorder that could, in the opinion of the Investigator, interfere with the absorption of ARQ 197 and/or erlotinib
  • Any other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation
  • 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
  • Known human immunodeficiency virus (HIV), or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  • Major surgical procedure within 4 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 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)
  • 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)
  • Known EGFR-mutation positive status

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Study site

    Atlanta, Georgia, 30341

  • Study site

    Baltimore, Maryland, 21205

  • Study site

    Boston, Massachusetts, 02114

  • Study site

    Burlington, Massachusetts, 01805

  • Study site

    Charleston, South Carolina, 29425

  • Study site

    Chicago, Illinois, 60611

  • Study site

    Dallas, Texas, 75390

  • Study site

    Kansas City, Kansas, 66160

  • Study site

    New York, New York, 10016

  • Study site

    Pittsburgh, Pennsylvania, 15232

  • Study site

    Stanford, California, 94305

  • Study site

    Washington D.C., District of Columbia, 20057

  • Study site

    Weston, Florida, 33331

Other trials in United States

About this study

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

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.

Read the 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 choice) single-agent chemotherapy agents including pemetrexed, docetaxel, or gemcitabine.

Being tested
ARQ 197 plus erlotinib, Pemetrexed, docetaxel or gemcitabine
Keywords
KRAS mutation, metastatic NSCLC
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ARQ 197 plus erlotinibDrug

    Also called Tivantinib

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

  • Pemetrexed, docetaxel or gemcitabineDrug

    Investigator's choice of a single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) administered according to the approved label.

Study groups in NCT01395758
Study groupRoleWhat they receive
tivantinib (ARQ 197) plus erlotinib armExperimentalEligible 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.
Receives: Drug: ARQ 197 plus erlotinib
Chemotherapy armActive comparatorInvestigator's choice of single agent chemotherapy (pemetrexed, docetaxel, or gemcitabine) administered in 3-week cycles according to the approved label until disease progression or unacceptable toxicity. Subjects who discontinued chemotherapy can be switched to the crossover arm (tivantinib plus erlotinib) and continue treatment until disease progression or unacceptable toxicity.
Receives: Drug: Pemetrexed, docetaxel or gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS) Among Subjects With KRAS Mutation Positive NSCLC (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Single Agent Chemotherapy.

    Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) criteria as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or progression of existing non-target lesions are also considered progression.

    Measured: Date of randomization until disease progression per RECIST (v 1.1) or death from any cause, whichever came first, assessed up to 24 months.

Secondary outcomes (3)

  1. Overall Survival (OS) Among All Eligible Subjects (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Chemotherapy.

    OS is calculated from the date of randomization until death from any cause.

    Measured: Date of randomization to the date of death from any cause, assessed up to 24 months

  2. Objective Response Rate (ORR) Among All Eligible Subjects (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Chemotherapy.

    Per RECIST v1.1, Complete Response (CR) = disappearance of all lesions and Partial Response (PR) = at least 30% decrease in the sum of diameters of target lesions. ORR = (CR+PR)/# subjects.

    Measured: 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

  3. ORR Among Subjects in the Crossover Period Treated With Erlotinib Plus Tivantinib

    Per RECIST v1.1, CR = disappearance of all lesions and PR = at least 30% decrease in the sum of diameters of target lesions. ORR = (CR+PR)/# subjects.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jul 2011 (estimated)
  2. Study startJul 2011
  3. Primary completionAug 2016
  4. Study completionAug 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
96 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01395758
Sponsor's protocol ID
ARQ 197-218
Status last verified
Mar 2018
First submitted
1 Jul 2011
Last updated
3 Apr 2018
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ARQ 197 plus erlotinib and Pemetrexed, docetaxel or gemcitabine in people with Metastatic Non-Small Cell Lung Cancer, run by ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) Among Subjects With KRAS Mutation Positive NSCLC (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Single Agent Chemotherapy. (time frame: Date of randomization until disease progression per RECIST (v 1.1) or death from any cause, whichever came first, assessed up to 24 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01395758.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2018.

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