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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kadmon Corporation, LLC
ClinicalTrials.gov Identifier:
NCT00364780
First received: August 14, 2006
Last updated: January 24, 2012
Last verified: January 2012
  Purpose

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).


Condition Intervention Phase
Non-small-cell Lung Cancer
Drug: XL647
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of XL647 in Subjects With Non-Small-Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Kadmon Corporation, LLC:

Primary Outcome Measures:
  • Response rate [ Time Frame: Inclusion until disease progression ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: Inclusion until 30 days post last treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Inclusion until disease progression or death ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Inclusion until disease progression ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Inclusion until 180-Day Follow-up post last treatment ] [ Designated as safety issue: No ]
  • Pharmacokinetic and pharmacodynamic parameters [ Time Frame: At various time points from pre-dosing until post dosing ] [ Designated as safety issue: Yes ]

Enrollment: 55
Study Start Date: July 2006
Study Completion Date: August 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Patients received XL647 at an intermittent dosing schedule receiving drug for 5 days followed by 9 days without drug.
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.
Experimental: 2
Patients received drug at a daily dosing schedule
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00364780

Locations
United States, Florida
Hematology Oncology Associates of the Treasure Coast
Port St. Lucie, Florida, United States, 34952
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Carle Cancer Center
Urbana, Illinois, United States, 61801
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
Wayne University, Wertz Clinical Cancer Center, Karmanos Center
Detroit, Michigan, United States, 48201
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
United States, Ohio
Case Western Reserve University, University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Kadmon Corporation, LLC
  More Information

No publications provided

Responsible Party: Kadmon Corporation, LLC
ClinicalTrials.gov Identifier: NCT00364780     History of Changes
Other Study ID Numbers: XL647-201
Study First Received: August 14, 2006
Last Updated: January 24, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms

ClinicalTrials.gov processed this record on October 19, 2014