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Pharmacodynamic Study of Sunitinib Malate in Patients With Renal Cell Cancer and Other Advanced Solid Malignancies

Phase 1
18 Years
Open (Enrolling)
Clear Cell Renal Cell Carcinoma, Recurrent Renal Cell Cancer, Stage III Renal Cell Cancer, Stage IV Renal Cell Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Pharmacodynamic Study of Sunitinib Malate in Patients With Renal Cell Cancer and Other Advanced Solid Malignancies


I. Determine the pharmacodynamic change using functional imaging (3'-deoxy-3'-[18F]
fluorothymidine [FLT]-PET/CT scans) in patients with unresectable or metastatic clear cell
renal cell carcinoma or other advanced solid malignancies treated with two different
schedules of sunitinib malate.

II. Evaluate the objective response in patients treated with this drug.


I. Measure the change in plasma VEGF levels and plasma HIF1-α levels as a potential
mechanism for VEGFR tyrosine kinase inhibitor (TKI) failure and rapid tumor growth following
VEGFR TKI withdrawal in these patients.

II. Correlate pharmacokinetics of this drug with response, unexpected toxicity, VEGF levels,
HIF1-α levels, and FLT-PET/CT scan changes.

OUTLINE: Patients are assigned to 1 of 2 different treatment schedules of sunitinib malate.

SCHEDULE A: Patients receive oral sunitinib malate once daily in weeks 1-4. Treatment
repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

SCHEDULE B: Patients receive oral sunitinib malate once daily in weeks 1, 2, 4, and 5.
Treatment repeats every 6 weeks in the absence of disease progression or unacceptable

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed renal cell cancer; or
other solid malignancy (excluding lymphoma) that is metastatic or unresectable and
for which no standard curative therapy exists

- For the renal cell cancer subset, a component of clear cell histology is

- Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by
conventional techniques or >= 10 mm by spiral CT scan

- Life expectancy > 12 weeks

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Leukocytes >= 3,000/mm^3

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- Hemoglobin >= 9 g/dL

- Serum calcium =< 12.0 mg/dL

- Total bilirubin normal

- Aspartate aminotransferase (AST) (serum glutamic oxalo-acetic transaminase [SGOT])
and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =<
2.5 times upper limit of normal (ULN), unless subjects have liver metastases, in
which case both AST and ALT must be =< 5 x ULN

- Creatinine =< 2 times ULN OR creatinine clearance >= 40 mL/min for patients with
creatinine levels above 2 x institutional normal

- All patients need to be willing to undergo planned pharmacodynamic assessments,
including serial PET imaging, plasma markers, and pharmacokinetic sampling

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy, radiotherapy, experimental therapy or major
surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering
the study or those who have not recovered (to grade < 1 or baseline) from clinically
significant adverse events due to agents administered more than 4 weeks earlier
(alopecia and fatigue excluded); clinical significance to be determined by

- Patients may not be receiving any other investigational agents

- No prior treatment with an anti-VEGF agent allowed

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to sunitinib malate

- Patients with QTc prolongation (defined as a QTc interval greater than 500 msec) or
other significant ECG abnormalities (per investigator discretion) are excluded

- Patients with poorly controlled hypertension (systolic blood pressure of 140 mm Hg or
higher or diastolic blood pressure of 90 mm Hg or higher) are ineligible

- Patients with any condition (e.g., gastrointestinal tract disease resulting in an
inability to take oral medication or a requirement for IV alimentation, prior
surgical procedures affecting absorption, or active peptic ulcer disease) that
impairs their ability to swallow and retain sunitinib tablets are excluded

- Patients with any of the following conditions are excluded:

- Serious or nonhealing wound, ulcer, or bone fracture

- Abdominal fistula, GI perforation, or intra-abdominal abscess within the past 28

- Cerebrovascular accident (CVA) or transient ischemic attack within 12 months
prior to study entry

- History of myocardial infarction, cardiac arrhythmia, stable/unstable angina,
symptomatic congestive heart failure, or coronary/peripheral artery bypass graft
or stenting within the past 12 months

- History of pulmonary embolism within the past 12 months

- Class III or IV heart failure as defined by the New York Heart Association
(NYHA) functional classification system

- Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid
function in the normal range with medication are ineligible; patients with a history
of hypothyroidism are eligible provided they are currently euthyroid

- Patients with known brain metastases

- Patients with uncontrolled intercurrent illness including, but not limited to,
ongoing or active infections or psychiatric illness/social situations that would
limit compliance with study requirements are ineligible

- Pregnant or breastfeeding

- No concurrent therapeutic doses of coumarin-derivative anticoagulants, such as
warfarin; Concurrent doses =< 2 mg/day allowed for prophylaxis of thrombosis,
Concurrent low molecular weight heparin allowed provided PT INR =< 1.5

- No concurrent agents with proarrhythmic potential (terfenadine, quinidine,
procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone,
indapamide, and flecainide acetate)

- HIV-positive patients on combination antiretroviral therapy are ineligible

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Standard uptake value as measured by 3'-deoxy-3'-[18F] fluorothymidine (FLT)-PET/CT scans

Outcome Time Frame:

Up to 3 years

Safety Issue:


Principal Investigator

Glenn Liu

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Wisconsin Hospital and Clinics


United States: Food and Drug Administration

Study ID:




Start Date:

May 2007

Completion Date:

Related Keywords:

  • Clear Cell Renal Cell Carcinoma
  • Recurrent Renal Cell Cancer
  • Stage III Renal Cell Cancer
  • Stage IV Renal Cell Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Carcinoma
  • Carcinoma, Renal Cell



University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001