Pharmacodynamic Study of Sunitinib Malate in Patients With Renal Cell Cancer and Other Advanced Solid Malignancies
Overview
- Phase
- Phase 1
- Intervention
- Computed Tomography
- Conditions
- Adult Solid Neoplasm
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Objective response
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This phase I trial is studying the side effects and best way to give sunitinib malate in treating patients with unresectable or metastatic kidney cancer or other advanced solid tumors. Sunitinib malate may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the pharmacodynamic change using functional imaging (3'-deoxy-3'-\[18F\] fluorothymidine \[FLT\]-positron emission tomography \[PET\]/computed tomography \[CT\] 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. SECONDARY OBJECTIVES: I. Measure the change in plasma vascular endothelial growth factor (VEGF) levels and plasma hypoxia-inducible factor (HIF)1-alpha levels as a potential mechanism for vascular endothelial growth factor receptor (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-alpha 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 sunitinib malate orally (PO) once daily (QD) in weeks 1-4. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. SCHEDULE B: Patients receive sunitinib malate PO QD in weeks 1, 2, 4, and 5. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Investigators
Eligibility Criteria
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 required
- •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
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 investigator
- •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 electrocardiogram (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, gastrointestinal (GI) perforation, or intra-abdominal abscess within the past 28 days
Arms & Interventions
Schedule A
Patients receive sunitinib malate PO QD in weeks 1-4. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Computed Tomography
Schedule A
Patients receive sunitinib malate PO QD in weeks 1-4. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Fluorothymidine F-18
Schedule A
Patients receive sunitinib malate PO QD in weeks 1-4. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Schedule A
Patients receive sunitinib malate PO QD in weeks 1-4. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Pharmacological Study
Schedule A
Patients receive sunitinib malate PO QD in weeks 1-4. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Positron Emission Tomography
Schedule A
Patients receive sunitinib malate PO QD in weeks 1-4. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Sunitinib Malate
Schedule B
Patients receive sunitinib malate PO QD in weeks 1, 2, 4, and 5. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Computed Tomography
Schedule B
Patients receive sunitinib malate PO QD in weeks 1, 2, 4, and 5. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Fluorothymidine F-18
Schedule B
Patients receive sunitinib malate PO QD in weeks 1, 2, 4, and 5. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Pharmacological Study
Schedule B
Patients receive sunitinib malate PO QD in weeks 1, 2, 4, and 5. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Positron Emission Tomography
Schedule B
Patients receive sunitinib malate PO QD in weeks 1, 2, 4, and 5. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: Sunitinib Malate
Outcomes
Primary Outcomes
Objective response
Time Frame: Up to 3 years
Standard uptake value as measured by 3'-deoxy-3'-[18F] fluorothymidine (FLT)-PET/CT scans
Time Frame: Up to 3 years
Plasma VEGF and HIF1-alpha levels
Time Frame: Up to 3 years
Secondary Outcomes
- Pharmacokinetic parameters (Cmax, Tmax, AUC, T1/2, and CL)(Up to 3 years)