Clinical Trials/NCT01244191

NCT01244191

Terminated

Phase 3

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of ARQ197 Plus Erlotinib Versus Placebo Plus Erlotinib in Previously Treated Subjects With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer (NSCLC)

Daiichi Sankyo0 sites1,048 target enrollmentJanuary 11, 2011

ConditionsNon Squamous, Non-small-cell Lung Cancer

InterventionsTivantinib Erlotinib Placebo

DrugsTivantinib Placebo Erlotinib

Overview

Phase: Phase 3
Intervention: Tivantinib
Conditions: Non Squamous, Non-small-cell Lung Cancer
Sponsor: Daiichi Sankyo
Enrollment: 1048
Primary Endpoint: Overall Survival Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer
Status: Terminated
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

This study is to determine if the combination regimen of tivantinib with erlotinib will improve overall survival relative to erlotinib alone in subjects with locally advanced or metastatic non-squamous, non-small cell lung cancer who have received 1 or 2 prior systemic anti-cancer therapies.

Registry

clinicaltrials.gov

Start Date

January 11, 2011

End Date

December 15, 2012

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Daiichi Sankyo

Responsible Party

Sponsor

Eligibility Criteria

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 1.
•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 complications.
•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.

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 randomization.
•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.

Arms & Interventions

Tivantinib and erlotinib

Tivantinib 720 mg daily (360 mg twice a day) in combination with 150 mg of erlotinib, given once a day

Intervention: Tivantinib

Tivantinib and erlotinib

Tivantinib 720 mg daily (360 mg twice a day) in combination with 150 mg of erlotinib, given once a day

Intervention: Erlotinib

Placebo and erlotinib

Tivantinib placebo given twice a day in combination with 150 mg of erlotinib, given once a day

Intervention: Placebo

Placebo and erlotinib

Tivantinib placebo given twice a day in combination with 150 mg of erlotinib, given once a day

Intervention: Erlotinib

Outcomes

Primary Outcomes

Overall Survival Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer

Time Frame: Date of randomization up to date of death, up to approximately 1 year 11 months postdose

The overall survival (OS) was defined as the time from the date of randomization to the date of death from any cause.

Secondary Outcomes

Overall Survival in the Epidermal Growth Factor Receptor Gene Wild-Type Subpopulation Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Non-Squamous NSCLC(Date of randomization up to date of death, up to approximately 1 year 11 months postdose)
Best Overall Tumor Response Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer(From baseline up to disease progression or the development of unacceptable toxicity (whichever occurs first), up to 1 year 11 months postdose)
Progression-free Survival Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer(Date of randomization to disease progression or death (whichever comes first), up to 1 year 11 months postdose)
Progression-free Survival in the Epidermal Growth Factor Receptor (EGFR) Gene Wild-Type Subpopulation Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants Non-Squamous NSCLC(Date of randomization to disease progression or death (whichever comes first), up to 1 year 11 months postdose)
Duration of Response Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer(From the date of first objective response (CR or PR) or SD to date of progressive disease, up to 1 year 11 months postdose)
Treatment-Emergent Adverse Events Reported in ≥5% of Participants Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Non-Squamous, Non-Small-Cell Lung Cancer(Baseline up to 30 days after last dose, up to 1 year 11 months postdose)
Treatment-Emergent Adverse Events Related to Tivantinib/Placebo Experienced by ≥5% of Participants Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Non-Squamous NSCLC(Baseline up to 30 days after last dose, up to 1 year 11 months postdose)