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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

Phase 1
18 Years
Not Enrolling
Cancer, Non-Small-Cell Lung Cancer, Breast Cancer

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Trial Information

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

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

- Subjects in the MTD Expansion Cohort:

- Must have measurable disease per Response Evaluation Criteria in Solid Tumors

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety, tolerability, and maximum tolerated dose (MTD) of XL647 administered in combination with XL147 orally daily

Outcome Time Frame:

Assessed at periodic visits

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

June 2008

Completion Date:

December 2009

Related Keywords:

  • Cancer
  • Non-Small-Cell Lung Cancer
  • Breast Cancer
  • Solid tumors
  • Breast Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Memorial Sloan Kettering Cancer Center New York, New York  10021
South Texas Accelerated Research Therapeutics San Antonio, Texas  78229