Clinical trial NCT00364780: Study of XL647 in Subjects With Non-Small-Cell Lung Cancer
Official title: A Phase 2 Study of XL647 in Subjects With Non-Small-Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-small-cell Lung Cancer
Lead sponsor: Kadmon Corporation, LLC
Sponsor class: INDUSTRY
First posted: 2006-08-16
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Response rate
timeFrame: Inclusion until disease progression
measure: Safety and tolerability
timeFrame: Inclusion until 30 days post last treatment
Secondary outcomes:
measure: Progression-free survival
timeFrame: Inclusion until disease progression or death
measure: Duration of response
timeFrame: Inclusion until disease progression
measure: Overall survival
timeFrame: Inclusion until 180-Day Follow-up post last treatment
measure: Pharmacokinetic and pharmacodynamic parameters
timeFrame: At various time points from pre-dosing until post dosing
Other outcomes:
Locations:
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates of the Treasure Coast
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Wayne University, Wertz Clinical Cancer Center, Karmanos Center
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve University, University Hospitals of Cleveland
state: Ohio
Study officials:
References:
citation: Pietanza MC, Gadgeel SM, Dowlati A, Lynch TJ, Salgia R, Rowland KM Jr, Wertheim MS, Price KA, Riely GJ, Azzoli CG, Miller VA, Krug LM, Kris MG, Beumer JH, Tonda M, Mitchell B, Rizvi NA. Phase II study of the multitargeted tyrosine kinase inhibitor XL647 in patients with non-small-cell lung cancer. J Thorac Oncol. 2012 May;7(5):856-65. doi: 10.1097/JTO.0b013e31824c943f.