A Randomized Phase 2 Study of Erlotinib + ARQ 197 Versus Erlotinib + Placebo in Previously Treated Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

NCT00777309 | Completed Phase 2

• 1 other identifier: ARQ 197-209
• Study Type: interventional
• Target: 167
• Locations: 6 countries
• Sites: 38

Brief Summary

This is a randomized, placebo-controlled, double blind phase 2 study designed to compare treatment with ARQ 197 plus erlotinib to erlotinib plus placebo in patients with non-small cell lung cancer. The study will enroll patients who have had one prior chemotherapy regimen (other than erlotinib) for NSCLC.

Conditions

Non Small Cell Lung Cancer

Keywords

NSCLC

Outcome Measures

Primary Outcomes (1)

• Evaluate progression free survival (PFS) in patients treated with erlotinib plus ARQ 197 versus erlotinib plus placebo

Secondary Outcomes (3)

• Evaluate overall survival (OS)

• Overall response rate (ORR)

• Safety of ARQ 197 in combination with erlotinib in patients with NSCLC

Study Arms (2)

1

EXPERIMENTAL

Erlotinib (150 mg) once daily plus ARQ 197 (360 mg) twice daily.

Drug: ARQ 197; Drug: Erlotinib

2

ACTIVE COMPARATOR

Erlotinib (150 mg) once daily plus ARQ 197 placebo twice daily

Drug: Erlotinib; Drug: Placebo

Interventions

ARQ 197 DRUG

360 mg administered twice daily until disease progression, unacceptable toxicity or other discontinuation criterion is met

Also known as: Tivantinib

1

Erlotinib DRUG

Erlotinib is a white, film coated tablet in strengths of 25, 100 and 150 mg administered once daily until disease progression, unacceptable toxicity or other discontinuation criterion is met.

Also known as: Tarceva

1; 2

Placebo DRUG

The placebo is provided as a capsule

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide signed and dated informed consent prior to study-specific screening procedures
• ≥ 18 years old
• Histologically or cytologically confirmed inoperable locally advanced or metastatic (stage IIIB/IV) NSCLC
• ≥ one prior chemotherapy regimen (including adjuvant chemotherapy)(not to have included erlotinib or other EGFR inhibiting agent)
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Male or female patients 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
• Good organ function
• Confirmed availability of archival pathology samples (10 unstained paraffin-embedded slides) or tissue block suitable for subsequent analysis of KRAS, EGFR, and c-Met

You may not qualify if:

• Previous receipt of erlotinib or other EGFR inhibiting therapy
• Receipt of any anti-tumor treatment for NSCLC within 4 weeks (2 weeks for radiotherapy) prior to the start of designated treatment
• Documented major surgical procedure within 4 weeks prior to randomization.
• Symptomatic central nervous system metastases either considered in the opinion of investigator to be clinically unstable or which require steroids, anti-epileptics, or other symptom-relieving medications
• Pregnant, breast-feeding, or refusing double barrier contraception, oral contraceptives or avoidance of pregnancy measures
• Significant gastrointestinal disorder that, in opinion of Investigator, could interfere with the absorption of ARQ 197 and/or erlotinib (e.g. Crohn's disease, small or large bowel resection, malabsorbtion syndrome)
• Unable or unwilling to swallow the complete dose of erlotinib or ARQ 197
• Any known contraindication to treatment with ARQ 197 or erlotinib
• Any known hypersensitivity to any of component of ARQ 197 or erlotinib
• Other malignancy within 5 years of randomization, 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
• Previously diagnosed grade 3 or 4 (CTCAE) bradycardia or other heart arrhythmia
• Any other significant co-mormid condition that, in opinion of the Investigator, would impair study participation or cooperation
• Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

Sponsors & Collaborators

• ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA): lead

Study Sites (38)

Unknown Facility

Burbank, California, 91505, United States

Location

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Santa Monica, California, 90404, United States

Location

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Torrington, Connecticut, 06790, United States

Location

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Jacksonville, Florida, 32204, United States

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Atlanta, Georgia, 30309, United States

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Chicago, Illinois, 60612, United States

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Batesville, Indiana, 47006, United States

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Indianapolis, Indiana, 46107, United States

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Louisville, Kentucky, 40202, United States

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Boston, Massachusetts, 02114, United States

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Worcester, Massachusetts, 01608, United States

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Charlotte, North Carolina, 28204, United States

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Canton, Ohio, 44718, United States

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Corpus Christi, Texas, 78410, United States

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Dallas, Texas, 75246, United States

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Dallas, Texas, 75390, United States

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Houston, Texas, 77024, United States

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Salt Lake City, Utah, 84114, United States

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Gauting, 82131, Germany

Location

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Großhansdorf, 22927, Germany

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Hamburg, 21075, Germany

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Mainz, 55131, Germany

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Mannheim, 68167, Germany

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Villingen-Schwenningen, 78050, Germany

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Daugavpils, 5420, Latvia

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Riga, 1002, Latvia

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Bialystock, 15-027, Poland

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Otwock, 05-400, Poland

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Poznan, 60-569, Poland

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Szczecin, 70-891, Poland

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Torun, 87-100, Poland

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Wroclaw, 53-439, Poland

Location

Central Clinical Hospital #1

Moscow, 125367, Russia

Location

Central Clinical Hospital #2

Moscow, 129128, Russia

Location

Unknown Facility

Saint Petersburg, 197002, Russia

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Unknown Facility

Saint Petersburg, 197089, Russia

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Unknown Facility

Saint Petersgurg, 197758, Russia

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Unknown Facility

Lviv, 79031, Ukraine

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

ARQ 197; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2008
• First Posted: October 22, 2008
• Study Start: September 1, 2008
• Primary Completion: May 1, 2011
• Study Completion: August 1, 2011
• Last Updated: February 28, 2013

Record last verified: 2013-02

Locations

DE (6); RU (5); UA (1); LA (2); PL (6); US (18)