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)

Phase 2

Completed

• Conditions: Non Small Cell Lung Cancer
• Interventions: Drug: ARQ 197; Drug: Placebo; Drug: Erlotinib

• Registration Number: NCT00777309
• Lead Sponsor: ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)

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.

Detailed Description

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. The study will evaluate progression-free survival between the two arms.

A total of 154 patients will be enrolled.

Study Timeline

• Study Start: 2008-09
• Study First Submitted: 2008-10-21
• Study First Submitted QC: 2008-10-21
• Study First Posted: 2008-10-22
• Primary Completion: 2011-05
• Study Completion: 2011-08
• Status Verified: 2013-02
• Disposition First Submitted: 2013-02-06
• Disposition First Submitted QC: 2013-02-06
• Disposition First Posted: 2013-02-08
• Last Update Submitted: 2013-02-22
• Last Update Posted: 2013-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 167

Inclusion Criteria

1. Provide signed and dated informed consent prior to study-specific screening procedures
2. ≥ 18 years old
3. Histologically or cytologically confirmed inoperable locally advanced or metastatic (stage IIIB/IV) NSCLC
4. ≥ one prior chemotherapy regimen (including adjuvant chemotherapy)(not to have included erlotinib or other EGFR inhibiting agent)
5. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
7. 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
8. Females of childbearing potential must have a negative serum pregnancy test
9. Good organ function
10. Confirmed availability of archival pathology samples (10 unstained paraffin-embedded slides) or tissue block suitable for subsequent analysis of KRAS, EGFR, and c-Met

Exclusion Criteria

1. Previous receipt of erlotinib or other EGFR inhibiting therapy
2. Receipt of any anti-tumor treatment for NSCLC within 4 weeks (2 weeks for radiotherapy) prior to the start of designated treatment
3. Documented major surgical procedure within 4 weeks prior to randomization.
4. 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
5. Pregnant, breast-feeding, or refusing double barrier contraception, oral contraceptives or avoidance of pregnancy measures
6. 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)
7. Unable or unwilling to swallow the complete dose of erlotinib or ARQ 197
8. Any known contraindication to treatment with ARQ 197 or erlotinib
9. Any known hypersensitivity to any of component of ARQ 197 or erlotinib
10. 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
11. Previously diagnosed grade 3 or 4 (CTCAE) bradycardia or other heart arrhythmia
12. Any other significant co-mormid condition that, in opinion of the Investigator, would impair study participation or cooperation
13. Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Placebo	Erlotinib (150 mg) once daily plus ARQ 197 placebo twice daily
1	Erlotinib	Erlotinib (150 mg) once daily plus ARQ 197 (360 mg) twice daily.
1	ARQ 197	Erlotinib (150 mg) once daily plus ARQ 197 (360 mg) twice daily.
2	Erlotinib	Erlotinib (150 mg) once daily plus ARQ 197 placebo twice daily

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Safety of ARQ 197 in combination with erlotinib in patients with NSCLC
Overall response rate (ORR)
Evaluate overall survival (OS)

Trial Locations

Locations (2)

Central Clinical Hospital #2; 🇷🇺 Moscow, Russian Federation

Central Clinical Hospital #1; 🇷🇺 Moscow, Russian Federation