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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00717587
First received: July 16, 2008
Last updated: January 9, 2014
Last verified: January 2009
  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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor regression as assessed by RECIST criteria [ Designated as safety issue: No ]

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
Investigators
Principal Investigator: Keith T. Flaherty, MD Abramson Cancer Center of the University of Pennsylvania
  More Information

Additional Information:
No publications provided

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
Study First Received: July 16, 2008
Last Updated: January 9, 2014
Health Authority: Unspecified

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

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Kidney Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Motexafin gadolinium
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Contrast Media
Dermatologic Agents
Diagnostic Uses of Chemicals
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Photosensitizing Agents
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014