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

This study has suspended participant recruitment.
(Study not initiated)
Sponsor:
Information provided by:
Exelixis
ClinicalTrials.gov Identifier:
NCT00704392
First received: June 20, 2008
Last updated: October 20, 2008
Last verified: October 2008
  Purpose

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 Intervention Phase
Cancer
Non-Small-Cell Lung Cancer
Breast Cancer
Drug: XL647
Drug: XL147
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Exelixis:

Primary Outcome Measures:
  • Safety, tolerability, and maximum tolerated dose (MTD) of XL647 administered in combination with XL147 orally daily [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Characterize pharmacokinetic parameters of XL647 administered in combination with XL147 daily in subjects with solid tumors [ Time Frame: Assessed at periodic visits ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 68
Study Start Date: June 2008
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00704392

Locations
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
Exelixis
  More Information

No publications provided

Responsible Party: Ronald Shazer, MD/Associate Director, Clinical Research, Exelixis, Inc.
ClinicalTrials.gov Identifier: NCT00704392     History of Changes
Other Study ID Numbers: XL647-003
Study First Received: June 20, 2008
Last Updated: October 20, 2008
Health Authority: United States: Food and Drug Administration

Keywords provided by Exelixis:
Solid tumors
NSCLC

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 24, 2014