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Safety Study of XL647 and XL147 Administered in Combination Daily in Adults With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00704392
Recruitment Status : Withdrawn (Study not initiated)
First Posted : June 24, 2008
Last Update Posted : August 20, 2015
Information provided by:

Brief Summary:
The purpose of this study is to determine the safety, tolerability, and highest safe doses of XL647 in combination with XL147 in adults with solid tumors. XL647 is a small molecule that potently inhibits multiple receptor kinases, including EGFR, VEGFR2 (KDR), and ErbB2. XL147 is a new chemical entity that inhibits PI3 Kinase. Inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells.

Condition or disease Intervention/treatment Phase
Cancer Non-small-cell Lung Cancer Breast Cancer Drug: XL647 Drug: XL147 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of XL647 and XL147 Administered in Combination Daily to Subjects With Solid Tumors
Study Start Date : June 2008
Estimated Primary Completion Date : December 2009
Estimated Study Completion Date : December 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 1 Drug: XL647
Tablets supplied at 50-mg strength administered orally daily

Drug: XL147
Gelatin capsules supplied at 25-mg and 100-mg strengths administered orally daily

Primary Outcome Measures :
  1. Safety, tolerability, and maximum tolerated dose (MTD) of XL647 administered in combination with XL147 orally daily [ Time Frame: Assessed at periodic visits ]

Secondary Outcome Measures :
  1. Characterize pharmacokinetic parameters of XL647 administered in combination with XL147 daily in subjects with solid tumors [ Time Frame: Assessed at periodic visits ]
  2. Assess pharmacodynamic effects of the XL647 and XL147 combination regimen at the highest safe dose of these agents in subjects with non-small-cell lung cancer or breast cancer [ Time Frame: Assessed at periodic visits ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • The subject has a histologically confirmed solid tumor that is metastatic or unresectable and is no longer responding to therapies known to prolong survival or to other standard therapies, or has disease for which no standard therapy exists.
  • The subject is ≥ 18 years old.
  • The subject's weight is ≥ 50 kg.
  • The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • The subject has a life expectancy of ≥ 3 months.
  • The subject has adequate organ and marrow function.
  • The subject has a fasting plasma glucose (FPG) < 120 mg/dL at screening.
  • The subject is capable of understanding and complying with the protocol and has signed the informed consent document.
  • Sexually active subjects (male and female) must agree to use accepted methods of contraception during the course of the study and for 3 months after the last dose of protocol drug(s).
  • Female subjects of childbearing potential must have a negative pregnancy test at screening.
  • Subjects in the MTD Expansion Cohort:

    • Must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST).
    • Must have a histologically confirmed diagnosis of NSCLC (Stage IIIB or IV) OR a histologically confirmed diagnosis of metastatic breast cancer.

Exclusion Criteria:

  • The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3 weeks (or nitrosoureas or mitomycin C within 6 weeks) before the first dose of XL647.
  • The subject has received prior treatment with a small molecule kinase inhibitor (including an investigational kinase inhibitor) within 14 days before the first dose of XL647.
  • The subject has received any other type of investigational agent within 30 days before the first dose of study treatment.
  • The subject has not recovered from toxicity due to prior therapy.
  • The subject has had major surgery within 30 days before the first dose of study drug. Subjects must have recovered or stabilized from prior surgery.
  • The subject is known to have diabetes.
  • The subject is currently receiving anticoagulation with warfarin (low-dose warfarin ≤ 1mg/day, heparin, and low-molecular weight heparins are permitted).
  • The subject has prothrombin time (PT)/International Normalized Ratio (INR) and /or partial thromboplastin time (PTT) test results at screening that are above 1.3 times the laboratory upper limit of normal.
  • The subject has any of the following cardiac criteria:

    • Corrected QT interval (QTc) of > 0.46 seconds
    • Has a finding of left bundle branch block
    • Has important bradycardia defined as a heart rate of < 50 bpm due to sinus node dysfunction
    • Has an obligate pacemaker
    • History of sustained ventricular arrhythmias (subjects with a history of atrial arrhythmias should be discussed with the sponsor before entry into the study)
    • Family history of congenital long QT syndrome or unexplained sudden death
    • Has uncontrolled hypertension
    • Has symptomatic congestive heart failure, unstable angina, or a myocardial infarction within the past 3 months
  • The subject requires treatment with drugs known to be associated with torsades de pointes or significant QT interval prolongation.
  • The subject has a serum potassium level or a serum magnesium level that falls outside the normal range.
  • The subject has known brain metastases or a primary brain tumor.
  • The subject has intercurrent illness including but not limited to ongoing or active infection.
  • The subject is known to be positive for the human immunodeficiency virus (HIV).
  • The subject is pregnant or breastfeeding.
  • The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulations
  • The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00704392

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United States, New York
Memorial Sloan Kettering Cancer Center
New York City, New York, United States, 10021
United States, Texas
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States, 78229
Sponsors and Collaborators

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Responsible Party: Ronald Shazer, MD/Associate Director, Clinical Research, Exelixis, Inc. Identifier: NCT00704392    
Other Study ID Numbers: XL647-003
First Posted: June 24, 2008    Key Record Dates
Last Update Posted: August 20, 2015
Last Verified: August 2015
Keywords provided by Exelixis:
Solid tumors
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action