Clinical trial NCT00777309: 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)
Official title: A Randomized Phase 2 Study of Erlotinib Plus ARQ 197 Versus Erlotinib Plus Placebo in Previously Treated Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: NSCLC
Lead sponsor: ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
Sponsor class: INDUSTRY
First posted: 2008-10-22
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluate progression free survival (PFS) in patients treated with erlotinib plus ARQ 197 versus erlotinib plus placebo
Secondary outcomes:
measure: Evaluate overall survival (OS)
measure: Overall response rate (ORR)
measure: Safety of ARQ 197 in combination with erlotinib in patients with NSCLC
Other outcomes:
Locations:
city: Burbank
country: United States
state: California
city: Santa Monica
country: United States
state: California
city: Torrington
country: United States
state: Connecticut
city: Jacksonville
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Batesville
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Louisville
country: United States
state: Kentucky
city: Boston
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Charlotte
country: United States
state: North Carolina
city: Canton
country: United States
state: Ohio
city: Corpus Christi
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Gauting
country: Germany
city: Grosshansdorf
country: Germany
city: Hamburg
country: Germany
city: Mainz
country: Germany
city: Mannheim
country: Germany
city: Villingen-Schwenningen
country: Germany
city: Daugavpils
country: Latvia
city: Riga
country: Latvia
city: Bialystock
country: Poland
city: Otwock
country: Poland
city: Poznan
country: Poland
city: Szczecin
country: Poland
city: Torun
country: Poland
city: Wroclaw
country: Poland
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital #1
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital #2
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersgurg
country: Russian Federation
city: Lviv
country: Ukraine
Study officials:
References: