Non-small-cell Lung Cancer
Conditions
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).
Interventions
DRUGXL647
XL647 will be administered orally as a single agent. XL647 will be supplied as 50 mg tablets. Subjects in the Intermittent 5 & 9 cohort will receive XL647 at a dose of 350 mg on a 5 days on and 9 days off cycle every 2 weeks for 8 weeks. Subjects in the Daily Dosing cohort will receive XL647 administered daily as a single oral dose of 300 mg. In the absence of progressive disease (PD) and unacceptable XL647-related toxicity, subjects may continue to receive XL647 treatment on their assigned dosing schedule for up to 1 year on this study. Subjects who reach 1 year of treatment with no evidence of disease progression may, with the concurrence of the investigator and the sponsor, continue to receive therapy.
Sponsors
Kadmon Corporation, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response rate | Inclusion until disease progression |
| Safety and tolerability | Inclusion until 30 days post last treatment |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Pharmacokinetic and pharmacodynamic parameters | At various time points from pre-dosing until post dosing |
Countries
United States
Outcome results
None listed