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

• ClinicalTrials.gov Identifier: NCT00364780
• Recruitment Status: Completed
• First Posted: August 16, 2006
• Last Update Posted: May 13, 2022
• Sponsor: Kadmon Corporation, LLC
• Information provided by (Responsible Party): Kadmon Corporation, LLC

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).

Condition or disease	Intervention/treatment	Phase
Non-small-cell Lung Cancer	Drug: XL647	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 55 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of XL647 in Subjects With Non-Small-Cell Lung Cancer
• Study Start Date: July 2006
• Actual Primary Completion Date: May 2010
• Actual Study Completion Date: August 2010

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Response rate [ Time Frame: Inclusion until disease progression ]
2. Safety and tolerability [ Time Frame: Inclusion until 30 days post last treatment ]

Secondary Outcome Measures :

1. Progression-free survival [ Time Frame: Inclusion until disease progression or death ]
2. Duration of response [ Time Frame: Inclusion until disease progression ]
3. Overall survival [ Time Frame: Inclusion until 180-Day Follow-up post last treatment ]
4. Pharmacokinetic and pharmacodynamic parameters [ Time Frame: At various time points from pre-dosing until post dosing ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Florida

Hematology Oncology Associates of the Treasure Coast

Port Saint 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

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.

• Responsible Party: Kadmon Corporation, LLC
• ClinicalTrials.gov Identifier: NCT00364780
• Other Study ID Numbers: XL647-201
• First Posted: August 16, 2006
• Last Update Posted: May 13, 2022
• Last Verified: May 2022

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; XL647; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action