Clinical trial NCT00589550: PEG-Interferon Alfa-2b and Sorafenib in Treating Patients With Unresectable or Metastatic Kidney Cancer
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).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Kidney Cancer
Keywords: clear cell renal cell carcinoma
stage III renal cell cancer
stage IV renal cell cancer
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Schering-Plough
First posted: 2008-01-09
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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)

Primary outcomes:
measure: Maximum Tolerated Dose of PEG-interferon Alfa-2b and Sorafenib Tosylate
timeFrame: up to 2 months
measure: Characterize the Toxicity of Peginterferon Alfa-2b and Sorafenib in Patients With Metastatic or Unresectable Clear Cell Renal Cell Carcinoma.
timeFrame: up to 2 months
Secondary outcomes:
measure: Progression-free Survival of Patients Receiving Peginterferon Alfa-2b and Sorafenib.
timeFrame: up to 1 year
measure: Response Rate of Patients Receiving Peginterferon Alfa-2b and Sorafenib.
timeFrame: up to 1 year
measure: Overall Survival
timeFrame: up to 1 year
measure: Activation of Interferon-induced Transcription Factors in Immune Cell Subsets by Flow Cytometry and Correlation of This Information With Clinical Outcome
timeFrame: up to 1 year
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
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Thomas E. Olencki, DO
role: STUDY_CHAIR
References: