Non Small Cell Lung Cancer
Conditions
Keywords
NSCLC
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.
Interventions
DRUGARQ 197
360 mg administered twice daily until disease progression, unacceptable toxicity or other discontinuation criterion is met
DRUGErlotinib
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.
DRUGPlacebo
The placebo is provided as a capsule
Sponsors
ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluate progression free survival (PFS) in patients treated with erlotinib plus ARQ 197 versus erlotinib plus placebo | — |
Secondary
| Measure | Time frame |
|---|---|
| Evaluate overall survival (OS) | — |
| Overall response rate (ORR) | — |
| Safety of ARQ 197 in combination with erlotinib in patients with NSCLC | — |
Countries
Germany, Latvia, Poland, Russia, Ukraine, United States
Outcome results
None listed