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

Non-small-cell Lung Cancer Clinical Trial

Official title:

A Phase 2 Study of XL647 in Subjects With Non-Small-Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00364780
• Other study ID #: XL647-201
• Status: Completed
• Phase: Phase 2
• Start date: July 2006
• Est. completion date: August 2010

Study information

• Verified date: May 2022
• Source: Kadmon Corporation, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: August 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small-cell Lung Cancer

Intervention

Drug:
• XL647
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.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	Case Western Reserve University, University Hospitals of Cleveland	Cleveland	Ohio
United States	Wayne University, Wertz Clinical Cancer Center, Karmanos Center	Detroit	Michigan
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida
United States	Carle Cancer Center	Urbana	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Kadmon Corporation, LLC

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate		Inclusion until disease progression
Primary	Safety and tolerability		Inclusion until 30 days post last treatment
Secondary	Progression-free survival		Inclusion until disease progression or death
Secondary	Duration of response		Inclusion until disease progression
Secondary	Overall survival		Inclusion until 180-Day Follow-up post last treatment
Secondary	Pharmacokinetic and pharmacodynamic parameters		At various time points from pre-dosing until post dosing