Study of XL647 in Subjects With Non-Small-Cell Lung Cancer

Phase 2

Completed

Brief Summary: The purpose of this phase II study is to determine the safety, tolerability, and activity of XL647 in previously untreated subjects with non-small cell lung cancer (NSCLC). XL647 is a small molecule that potently inhibits multiple receptor kinases, including EGFR, VEGFR2 (KDR), ErbB2, and EphB4. Sensitivity to EGFR inhibitors has been linked to specific EGFR mutations and associated with certain clinical characteristics in patients with NSCLC (eg, female, minimal and remote smoking history, and adenocarcinoma histology).

Recruitment & Eligibility

Inclusion Criteria

Subject has NSCLC with a histologically confirmed diagnosis of adenocarcinoma with measurable disease (stage IIIB, with malignant pleural effusion, and stage IV) and either has a demonstrated activating mutation of the EGF receptor in tumor tissue or meets one of three criteria: asian, female, and minimal or no smoking history.
Measurable disease defined according to RECIST
ECOG performance status of 0 or 1
Normal organ and marrow function
No other malignancies within 5 years, except for non-melanoma skin cancer

Exclusion Criteria

Radiation to ≥25% of bone marrow within 30 days of XL647 treatment
Prior systemic anticancer therapy, including cytotoxic chemotherapy, anti-VEGF, anti-VEGFR, or anti-EGFR agents or investigational drug
Subject has not recovered to ≤ grade 1 or to within 10% of baseline values from adverse events due to other medications administered > 30 days before study enrollment
Receiving anticoagulation therapy with warfarin (low-dose warfarin < 1 mg/day, heparin and low molecular weight heparins are permitted)
The subject meets any of the following cardiac criteria:
- Corrected QT interval (QTc) of > 460 msec
- Family history of congenital long QT syndrome or unexplained sudden death
- History of sustained ventricular arrhythmias
- Has a finding of left bundle branch block
- Has an obligate pacemaker
- Has important bradycardia defined as a heart rate of < 50 bpm due to sinus node dysfunction
- Has uncontrolled hypertension
- Has symptomatic congestive heart failure, unstable angina, or a myocardial infarction within the past 3 months
- Has a serum potassium or serum magnesium level that falls outside the normal range
The subject has progressive symptomatic or hemorrhagic brain or leptomeningeal metastases
Uncontrolled intercurrent illness
Subject is pregnant or breastfeeding
Known HIV

Arm && Interventions

Group	Intervention	Description
1	XL647	Patients received XL647 at an intermittent dosing schedule receiving drug for 5 days followed by 9 days without drug.
2	XL647	Patients received drug at a daily dosing schedule

Primary Outcome Measures

Name	Time	Method
Response rate	Inclusion until disease progression
Safety and tolerability	Inclusion until 30 days post last treatment

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic and pharmacodynamic parameters	At various time points from pre-dosing until post dosing
Progression-free survival	Inclusion until disease progression or death
Duration of response	Inclusion until disease progression
Overall survival	Inclusion until 180-Day Follow-up post last treatment

Locations (7): Hematology Oncology Associates of the Treasure Coast
🇺🇸
Port Saint Lucie, Florida, United States
Carle Cancer Center
🇺🇸
Urbana, Illinois, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Case Western Reserve University, University Hospitals of Cleveland
🇺🇸
Cleveland, Ohio, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Wayne University, Wertz Clinical Cancer Center, Karmanos Center
🇺🇸
Detroit, Michigan, United States