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

NCT00364780 | Completed Phase 2 DMC

• 1 other identifier: XL647-201
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 7

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).

Conditions

Non-small-cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Response rate

  Inclusion until disease progression

• Safety and tolerability

  Inclusion until 30 days post last treatment

Secondary Outcomes (4)

• Progression-free survival

  Inclusion until disease progression or death

• Duration of response

  Inclusion until disease progression

• 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

Study Arms (2)

1

EXPERIMENTAL

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

Drug: XL647

2

EXPERIMENTAL

Patients received drug at a daily dosing schedule

Drug: XL647

Interventions

XL647 DRUG

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.

1; 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kadmon Corporation, LLC: lead

Study Sites (7)

Hematology Oncology Associates of the Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Wayne University, Wertz Clinical Cancer Center, Karmanos Center

Detroit, Michigan, 48201, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Case Western Reserve University, University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Related 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.

  PMID: 22722787 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

XL647

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2006
• First Posted: August 16, 2006
• Study Start: July 1, 2006
• Primary Completion: May 1, 2010
• Study Completion: August 1, 2010
• Last Updated: May 13, 2022

Record last verified: 2022-05

Locations

US (7)