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Sunitinib Malate in Treating Patients With Unresectable or Metastatic Kidney Cancer or Other Advanced Solid Tumors

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00499135
First Posted: July 11, 2007
Last Update Posted: October 10, 2017
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.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
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.

Condition Intervention Phase
Adult Solid Neoplasm Clear Cell Renal Cell Carcinoma Recurrent Renal Cell Carcinoma Stage III Renal Cell Cancer Stage IV Renal Cell Cancer Other: Computed Tomography Other: Fluorothymidine F-18 Other: Laboratory Biomarker Analysis Other: Pharmacological Study Other: Positron Emission Tomography Drug: Sunitinib Malate Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacodynamic Study of Sunitinib Malate in Patients With Renal Cell Cancer and Other Advanced Solid Malignancies

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response [ Time Frame: Up to 3 years ]
  • Plasma VEGF and HIF1-alpha levels [ 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 ]

Secondary Outcome Measures:
  • Pharmacokinetic parameters (Cmax, Tmax, AUC, T1/2, and CL) [ Time Frame: Up to 3 years ]

Enrollment: 25
Actual Study Start Date: May 22, 2007
Study Completion Date: May 14, 2014
Primary Completion Date: May 14, 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Other: Computed Tomography
Correlative studies
Other Names:
  • CAT
  • CAT Scan
  • Computerized Axial Tomography
  • computerized tomography
  • CT
  • CT SCAN
  • tomography
Other: Fluorothymidine F-18
Correlative studies
Other Names:
  • 18F-FLT
  • 3'-deoxy-3'-(18F) fluorothymidine
  • 3'-deoxy-3'-[18F]fluorothymidine
  • fluorothymidine F 18
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Other: Positron Emission Tomography
Correlative studies
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • positron emission tomography scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
Drug: Sunitinib Malate
Given PO
Other Names:
  • SU011248
  • SU11248
  • sunitinib
  • Sutent
Experimental: 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.
Other: Computed Tomography
Correlative studies
Other Names:
  • CAT
  • CAT Scan
  • Computerized Axial Tomography
  • computerized tomography
  • CT
  • CT SCAN
  • tomography
Other: Fluorothymidine F-18
Correlative studies
Other Names:
  • 18F-FLT
  • 3'-deoxy-3'-(18F) fluorothymidine
  • 3'-deoxy-3'-[18F]fluorothymidine
  • fluorothymidine F 18
Other: Pharmacological Study
Correlative studies
Other: Positron Emission Tomography
Correlative studies
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • positron emission tomography scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
Drug: Sunitinib Malate
Given PO
Other Names:
  • SU011248
  • SU11248
  • sunitinib
  • Sutent

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.

  Eligibility

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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 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
    • 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 prothrombin time (PT) international normalized ratio ( INR) =< 1.5
  • No concurrent agents with proarrhythmic potential (terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, and flecainide acetate)
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT00499135


Locations
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Glenn Liu University of Wisconsin, Madison
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00499135     History of Changes
Other Study ID Numbers: NCI-2009-00245
NCI-2009-00245 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000552705
H-2007-0039
CO06902
CO 06902 ( Other Identifier: University of Wisconsin Hospital and Clinics )
7898 ( Other Identifier: CTEP )
P30CA014520 ( U.S. NIH Grant/Contract )
U01CA062491 ( U.S. NIH Grant/Contract )
First Submitted: July 10, 2007
First Posted: July 11, 2007
Last Update Posted: October 10, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sunitinib
Dideoxynucleosides
Alovudine
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents