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

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

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).

Study Overview

• Status: Completed
• Conditions: Non-small-cell Lung Cancer
• Intervention / Treatment: Drug: XL647

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Port Saint Lucie, Florida, United States, 34952
      • Hematology Oncology Associates of the Treasure Coast
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne University, Wertz Clinical Cancer Center, Karmanos Center
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University, University Hospitals of Cleveland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate	Inclusion until disease progression
Safety and tolerability	Inclusion until 30 days post last treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of response	Inclusion until disease progression
Progression-free survival	Inclusion until disease progression or death
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

Collaborators and Investigators

• Sponsor: Kadmon Corporation, LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: August 14, 2006
• First Submitted That Met QC Criteria: August 14, 2006
• First Posted (Estimate): August 16, 2006

Study Record Updates

• Last Update Posted (Actual): May 13, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; XL647
• Other Study ID Numbers: XL647-201