PEG-Interferon Alfa-2b and Sorafenib in Treating Patients With Unresectable or Metastatic Kidney Cancer

This study has been terminated.
(low accrual)
Sponsor:
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
Thomas Olencki, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00589550
First received: January 5, 2008
Last updated: May 22, 2013
Last verified: May 2013
  Purpose

RATIONALE: PEG-interferon alfa-2b may interfere with the growth of tumor cells. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also stop the growth of kidney cancer by blocking blood flow to the tumor. Giving PEG-interferon alfa-2b together with sorafenib may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of PEG-interferon alfa-2b and sorafenib in treating patients with unresectable or metastatic kidney cancer.


Condition Intervention Phase
Kidney Cancer
Biological: PEG-interferon alfa-2b
Drug: Sorafenib
Genetic: gene expression analysis
Genetic: polymerase chain reaction
Genetic: reverse transcriptase-polymerase chain reaction
Other: flow cytometry
Other: immunoenzyme technique
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study Of Peginterferon Alfa-2b (PEG-INTRON) With Sorafenib (Nexavar) In Patients With Unresectable Or Metastatic Clear Cell Renal Carcinoma (RCC).

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose of PEG-interferon alfa-2b and sorafenib tosylate [ Time Frame: 2008-present ] [ Designated as safety issue: Yes ]
  • Characterize the toxicity of peginterferon alfa-2b and sorafenib in patients with metastatic or unresectable clear cell renal cell carcinoma. [ Time Frame: 2008-present ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free survival of patients receiving peginterferon alfa-2b and sorafenib. [ Time Frame: 2008-present ] [ Designated as safety issue: No ]
  • Response rate of patients receiving peginterferon alfa-2b and sorafenib. [ Time Frame: 2008-present ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2008-present ] [ Designated as safety issue: No ]
  • Activation of interferon-induced transcription factors in immune cell subsets by flow cytometry and correlation of this information with clinical outcome [ Time Frame: 2008-present ] [ Designated as safety issue: No ]
  • Circulating levels of IFN-γ and IL-5 for determination of Th1/Th2 status and CD4+, CD25+, and FoxP3 cell number (T regs) in peripheral blood [ Time Frame: 2008-present ] [ Designated as safety issue: No ]

Enrollment: 1
Study Start Date: February 2008
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Peginterferon alfa-2b
Peginterferon alfa-2b will be administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks.
Biological: PEG-interferon alfa-2b
administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks.
Other Name: peginterferon alfa-2b
Drug: Sorafenib
Other Names:
  • Nexavar
  • BAY 54-9085 is the tosylate salt of BAY 43-9006
Genetic: gene expression analysis Genetic: polymerase chain reaction Genetic: reverse transcriptase-polymerase chain reaction Other: flow cytometry Other: immunoenzyme technique Other: laboratory biomarker analysis

Detailed Description:

OBJECTIVES:

Primary

  • To determine the maximum tolerated dose and toxicity of PEG-interferon alfa-2b and sorafenib tosylate in patients with unresectable or metastatic clear cell renal cell carcinoma.

Secondary

  • To determine the progression-free survival of patients treated with this regimen.
  • To evaluate, in a preliminary manner, the response rate and overall survival of patients treated with this regimen.
  • To evaluate the activation of interferon-induced transcription factors in immune cell subsets (including regulatory T cells [T regs]) using a novel flow cytometric assay and correlate this information with clinical outcome.
  • To measure circulating levels of IFN-γ and IL-5 for determination of Th1/Th2 status and CD4+, CD25+, and FoxP3 cell number (T regs) in peripheral blood.

OUTLINE: Patients receive PEG-interferon alfa-2b subcutaneously on days 1, 8, 15, 22, 29, 36, 43, and 50. Patients also receive oral sorafenib tosylate 2-3 times daily on days 15-56 of course 1 and on days 1-56 of all subsequent courses. Courses repeat every 56 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and periodically during study for correlative laboratory studies. Peripheral blood mononuclear cells are analyzed for STAT proteins (STAT1, STAT2, STAT3, STAT4, STAT5) and CD4+, CD25+, and FoxP3 regulatory T cells by flow cytometric assays. Samples are also analyzed for the presence of VEGF, VEGFR, IFN-γ, and IL-5 by ELISA assays; baseline expression of Jak-STAT signaling intermediates (Jak1, Tyk2, IFNAR, and IRF9) by immunoblot analysis; and interferon-stimulated gene expression by real time PCR and RT-PCR analysis.

After completion of study therapy, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have histologically or cytologically confirmed clear cell renal cell carcinoma (RCC)
  • Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension and is ≥ 1.0 cm by spiral CT scan
  • No prior treatment except

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy > 6 months
  • Good/intermediate Motzer prognostic status
  • ANC ≥ 1,000/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10.0 g/dL
  • Total bilirubin ≤ 2.0 mg/dL
  • AST and ALT < 2.5 times normal
  • Creatinine ≤ 1.8 mg/dL OR creatinine clearance > 50 mL/min
  • Calcium < 12 mg/dL (when corrected for serum albumin)
  • INR < 1.5 times upper limit of normal
  • Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40% by 2D echo
  • Pulse oximetry ≥ 90% at rest on room air
  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No evidence of bleeding diathesis
  • No uncontrolled coagulation disorders
  • No active infections requiring IV antibiotics
  • No known HIV, hepatitis C, or hepatitis B
  • No autoimmune disease requiring ongoing therapy
  • No requirement for adrenal replacement
  • No angina (controlled or uncontrolled)
  • No uncontrolled hypertension
  • No history of other major medical illnesses including, but not limited to, any of the following:

    • Cardiac ischemia
    • Myocardial infarction
    • Major cardiac arrhythmias
    • Inflammatory bowel disorders
  • No other prior malignancy except for previously treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 3 years
  • No significant psychiatric disease that, in the opinion of the principal investigator, would preclude giving adequate informed consent or render immunotherapy unsafe

PRIOR CONCURRENT THERAPY:

  • No prior treatment for RCC except sunitinib malate

    • Patients may have progressed or have been intolerant to sunitinib malate
  • No prior systemic treatment for metastatic disease (other than sunitinib malate)
  • No prior organ allografts
  • At least 2 weeks since prior laparoscopic/robotic surgery
  • At least 4 weeks since prior open nephrectomy
  • More than 4 weeks since prior and no concurrent radiotherapy or other surgery
  • More than 4 weeks since prior systemic steroids
  • More than 2 weeks since prior topical, injected, or inhaled steroids
  • No concurrent steroid therapy
  • No concurrent Hypericum perforatum (St. John's wort)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00589550

Locations
United States, Ohio
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Thomas Olencki
Schering-Plough
Investigators
Study Chair: Thomas E. Olencki, DO Ohio State University Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Thomas Olencki, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00589550     History of Changes
Other Study ID Numbers: OSU-06113
Study First Received: January 5, 2008
Last Updated: May 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Ohio State University Comprehensive Cancer Center:
clear cell renal cell carcinoma
stage III renal cell cancer
stage IV renal cell cancer

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Interferon-alpha
Interferon Alfa-2a
Interferon Alfa-2b
Interferons
Peginterferon alfa-2b
Reaferon
Sorafenib
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 15, 2014