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

Primary Purpose

Non-small-cell Lung Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
XL647
Sponsored by
Kadmon Corporation, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small-cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hematology Oncology Associates of the Treasure Coast
  • University of Chicago
  • Carle Cancer Center
  • Massachusetts General Hospital
  • Wayne University, Wertz Clinical Cancer Center, Karmanos Center
  • Memorial Sloan Kettering Cancer Center
  • Case Western Reserve University, University Hospitals of Cleveland

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

1

2

Arm Description

Patients received XL647 at an intermittent dosing schedule receiving drug for 5 days followed by 9 days without drug.

Patients received drug at a daily dosing schedule

Outcomes

Primary Outcome Measures

Response rate
Safety and tolerability

Secondary Outcome Measures

Progression-free survival
Duration of response
Overall survival
Pharmacokinetic and pharmacodynamic parameters

Full Information

First Posted
August 14, 2006
Last Updated
May 9, 2022
Sponsor
Kadmon Corporation, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT00364780
Brief Title
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

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
July 2006 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
August 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kadmon Corporation, LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small-cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Patients received XL647 at an intermittent dosing schedule receiving drug for 5 days followed by 9 days without drug.
Arm Title
2
Arm Type
Experimental
Arm Description
Patients received drug at a daily dosing schedule
Intervention Type
Drug
Intervention Name(s)
XL647
Intervention Description
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.
Primary Outcome Measure Information:
Title
Response rate
Time Frame
Inclusion until disease progression
Title
Safety and tolerability
Time Frame
Inclusion until 30 days post last treatment
Secondary Outcome Measure Information:
Title
Progression-free survival
Time Frame
Inclusion until disease progression or death
Title
Duration of response
Time Frame
Inclusion until disease progression
Title
Overall survival
Time Frame
Inclusion until 180-Day Follow-up post last treatment
Title
Pharmacokinetic and pharmacodynamic parameters
Time Frame
At various time points from pre-dosing until post dosing

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Hematology Oncology Associates of the Treasure Coast
City
Port Saint Lucie
State/Province
Florida
ZIP/Postal Code
34952
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Carle Cancer Center
City
Urbana
State/Province
Illinois
ZIP/Postal Code
61801
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Wayne University, Wertz Clinical Cancer Center, Karmanos Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Case Western Reserve University, University Hospitals of Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22722787
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.
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Study of XL647 in Subjects With Non-Small-Cell Lung Cancer

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