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Sunitinib Before and After Surgery in Treating Patients With Stage IV Kidney Cancer

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified January 2009 by National Cancer Institute (NCI).
Recruitment status was:  Recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT00717587
First Posted: July 17, 2008
Last Update Posted: January 10, 2014
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.
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)
  Purpose

RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well sunitinib works when given before and after surgery in treating patients with stage IV kidney cancer.


Condition Intervention Phase
Kidney Cancer Drug: motexafin gadolinium Drug: sunitinib malate Genetic: comparative genomic hybridization Genetic: gene expression analysis Genetic: mutation analysis Genetic: polymorphism analysis Other: immunohistochemistry staining method Other: iodine I-124 girentuximab Other: laboratory biomarker analysis Other: pharmacological study Procedure: adjuvant therapy Procedure: neoadjuvant therapy Procedure: therapeutic conventional surgery Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Histopathologic and Imaging Study of Renal Cell Carcinoma Vasculature in the Setting of Sunitinib Therapy Prior to Cytoreductive Nephrectomy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression-free survival

Secondary Outcome Measures:
  • Tumor regression as assessed by RECIST criteria

Estimated Enrollment: 20
Study Start Date: June 2008
Estimated Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • To correlate histologic measures of tumor angiogenesis and VHL mutation/methylation status with clinical outcome in patients with stage IV renal cell carcinoma treated with sunitinib malate.
  • To determine the effects of sunitinib malate on tumor vascular permeability by dynamic contrast-enhanced MRI and iodine I 124 chimeric monoclonal antibody G250 positron emission tomography (PET) after 2 weeks of therapy.
  • To correlate steady-state plasma concentrations of sunitinib malate and angiogenic growth factors in serum with clinical outcome in these patients.

OUTLINE:

  • Neoadjuvant therapy:Patients receive oral sunitinib malate once daily on days 1-14.
  • Cytoreductive surgery: Patients undergo cytoreductive nephrectomy on day 16.
  • Adjuvant therapy:Beginning at least 4 weeks after surgery, patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days in the absence of disease progression or unacceptable toxicity.

Patients undergo dynamic contrast-enhanced MRI with motexafin gadolinium and positron emission tomography with iodine I 124 chimeric monoclonal antibody G250 at baseline and after completion of neoadjuvant sunitinib malate (prior to cytoreductive nephrectomy).

Patients undergo tumor tissue and blood sample collection periodically for correlative laboratory studies. Tumor tissue samples are analyzed for VHL mutations and other somatic genetic mutations by mutation analysis; allelic loss or gain by comparative genomic amplification; microvessel density (MVD) by immunohistochemical staining for CD34 and CD105; pERK, SMA, Ki-67, HIF-1α, CAIX, macrophage migration inhibition factor (MIF), and CREB by multicolor analysis; and VEGF-R1 and -R2 and other relevant antigen expression by validated assays. Blood samples are analyzed for pharmacokinetics; angiogenic growth factor levels (e.g., free VEGF, basic FGF, and other markers); and polymorphisms in VEGF, VEGFR, VHL, and HIF.

After completion of study treatment, patients are followed periodically.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of renal cell carcinoma

    • AJCC stage IV disease
  • Radiographic evidence of disease for which cytoreductive nephrectomy is deemed to be clinically indicated AND for which preoperative embolization is not deemed necessary by the surgeon
  • No history or clinical evidence of brain metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • WBC ≥ 3,000/mm³
  • Absolute granulocyte count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Serum creatinine ≤ 2.0 times upper limit of normal (ULN) OR serum creatinine clearance ≥ 40 mL/min
  • Total bilirubin ≤ 1.5 times ULN (< 3.0 times ULN in the presence of Gilbert's disease)
  • AST/ALT ≤ 2.5 times ULN (≤ 5.0 times ULN in the presence of liver metastases)
  • INR ≤ 1.5*
  • PTT normal*
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No pre-existing thyroid abnormality with thyroid-stimulating hormone that cannot be maintained in the normal range with medication
  • No hypertension that cannot be controlled by medications (i.e., diastolic BP ≥ 100 mm Hg despite optimal medical therapy)
  • No ongoing cardiac dysrhythmias ≥ grade 2 (according to NCI CTCAE v3.0)
  • No other concurrent malignancies
  • No concurrent serious illness including, but not limited to, any of the following:

    • Ongoing or active infection requiring parenteral antibiotics
    • Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, myocardial infarction, or unstable angina)
    • New York Heart Association class II-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Peripheral vascular disease ≥ grade 2 within the past year
    • Psychiatric illness/social situation that would limit compliance with study requirements NOTE: *Patients who are taking warfarin must have documentation of an INR ≤ 1.5 and PTT normal prior to the initiation of anticoagulation to rule out a baseline coagulopathy

PRIOR CONCURRENT THERAPY:

  • At least 2 weeks since prior radiotherapy and recovered
  • Prior radiotherapy to a symptomatic site of metastatic disease is allowed
  • No prior systemic therapy
  • No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort)
  • No other concurrent investigational agents
  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): NCT00717587


Locations
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104-4283
Contact: Clinical Trials Office - Abramson Cancer Center of the Univers    800-474-9892      
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
National Cancer Institute (NCI)
Investigators
Principal Investigator: Keith T. Flaherty, MD Abramson Cancer Center of the University of Pennsylvania
  More Information

Responsible Party: Keith T. Flaherty, Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00717587     History of Changes
Other Study ID Numbers: CDR0000600332
UPCC-10807
PFIZER-807184
First Submitted: July 16, 2008
First Posted: July 17, 2008
Last Update Posted: January 10, 2014
Last Verified: January 2009

Keywords provided by National Cancer Institute (NCI):
stage IV renal cell cancer
recurrent renal cell cancer

Additional relevant MeSH terms:
Kidney Neoplasms
Carcinoma, Renal Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Kidney Diseases
Urologic Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Sunitinib
Motexafin gadolinium
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Photosensitizing Agents
Dermatologic Agents