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

A Phase I Study Of Peginterferon Alfa-2b (PEG-INTRON) With Sorafenib (Nexavar) In Patients With Unresectable Or Metastatic Clear Cell Renal Carcinoma (RCC).

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.

Study Overview

• Status: Terminated
• Conditions: Kidney Cancer
• Intervention / Treatment: Genetic: gene expression analysis; Other: laboratory biomarker analysis; Other: immunoenzyme technique; Genetic: reverse transcriptase-polymerase chain reaction; Other: flow cytometry; Genetic: polymerase chain reaction; Drug: Sorafenib; Biological: PEG-interferon alfa-2b

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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.

Genetic: gene expression analysis; Other: laboratory biomarker analysis; Other: immunoenzyme technique; Genetic: reverse transcriptase-polymerase chain reaction; Other: flow cytometry; Genetic: polymerase chain reaction; Drug: Sorafenib; Other Names: Nexavar; BAY 54-9085 is the tosylate salt of BAY 43-9006; 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 Names: peginterferon alfa-2b

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose of PEG-interferon Alfa-2b and Sorafenib Tosylate	up to 2 months
Characterize the Toxicity of Peginterferon Alfa-2b and Sorafenib in Patients With Metastatic or Unresectable Clear Cell Renal Cell Carcinoma.	up to 2 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free Survival of Patients Receiving Peginterferon Alfa-2b and Sorafenib.	up to 1 year
Response Rate of Patients Receiving Peginterferon Alfa-2b and Sorafenib.	up to 1 year
Overall Survival	up to 1 year
Activation of Interferon-induced Transcription Factors in Immune Cell Subsets by Flow Cytometry and Correlation of This Information With Clinical Outcome	up to 1 year
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	Up to 1 year

Collaborators and Investigators

• Sponsor: Thomas Olencki
• Collaborators: Schering-Plough
• Investigators: Study Chair: Thomas E. Olencki, DO, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• Jamesline

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: January 5, 2008
• First Submitted That Met QC Criteria: January 5, 2008
• First Posted (Estimate): January 9, 2008

Study Record Updates

• Last Update Posted (Estimate): June 8, 2015
• Last Update Submitted That Met QC Criteria: June 4, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: stage IV renal cell cancer; stage III renal cell cancer; clear cell renal cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Protein Kinase Inhibitors; Interferons; Interferon-alpha; Sorafenib; Interferon alpha-2; Peginterferon alfa-2b
• Other Study ID Numbers: OSU-06113