Clinical trial NCT00467077: Gefitinib and PEG-Interferon Alfa-2b in Treating Patients With Unresectable or Metastatic Kidney Cancer
Official title: Phase II Trial of ZD1839 (IRESSA®) and Pegylated Interferon Alfa 2b (PEG-Intron™) in Unresectable or Metastatic Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Kidney Cancer
Keywords: recurrent renal cell cancer
stage IV renal cell cancer
stage III renal cell cancer
Lead sponsor: California Cancer Consortium
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-04-27
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Gefitinib may stop the growth of kidney cancer by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. PEG-interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of kidney cancer. Giving gefitinib together with PEG-interferon alfa-2b may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving gefitinib together with PEG-interferon alfa-2b works in treating patients with unresectable or metastatic kidney cancer.

Detailed description: OBJECTIVES:

Primary

* Determine the 6-month progression-free survival of patients with unresectable or metastatic renal cell carcinoma treated with gefitinib and PEG-interferon alfa-2b.

Secondary

* Determine the response rate (by RECIST criteria), duration of response, time to treatment failure, and overall survival of patients treated with this regimen.
* Assess toxicity and tolerability of this regimen in these patients.
* Determine the pre-treatment expression of the von Hippel-Lindau (VHL) protein, the epidermal growth factor receptor (EGFR), and p27, and correlate with response to treatment.
* Determine post-treatment alteration of EGFR and p27 expression in patients with tumors accessible for serial biopsy.
* Assess changes in EGFR levels in buccal epithelial cells in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral gefitinib once daily and PEG-interferon alfa-2b subcutaneously once weekly in weeks 1-6. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with a partial response or stable disease after completion of course 2 continue to receive gefitinib alone as above in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 2 years.

PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed renal cell carcinoma

  * Metastatic or advanced/unresectable disease
* Measurable or nonmeasurable disease as defined by RECIST criteria
* No uncontrolled brain metastases

  * Patients with adequately treated brain metastases who are not taking anticonvulsants and corticosteroids may be eligible

PATIENT CHARACTERISTICS:

* Karnofsky performance status 60-100%
* Life expectancy ≥ 12 weeks
* WBC ≥ 3,500/mm³
* Platelet count ≥ 100,000/mm³
* Absolute granulocyte count ≥ 1,500/mm³
* Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 50 mL/min
* Bilirubin ≤ 1.5 mg/dL
* AST ≤ 2 times upper limit of normal (ULN)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or adequately treated stage I or II cancer from which the patient is currently in complete remission
* No known severe hypersensitivity to gefitinib or its excipients
* No incomplete healing from previous oncologic or other major surgery
* No unresolved chronic toxicity \> grade 2 from previous anticancer therapy (except alopecia and anemia)
* No evidence of clinically active interstitial lung disease

  * Patients with chronic stable radiographic changes who are asymptomatic are eligible
* No evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
* No other significant clinical disorder or laboratory finding that would preclude study participation

PRIOR CONCURRENT THERAPY:

* More than 30 days since prior nonapproved or investigational drugs
* More than 6 weeks since prior aldesleukin or interferon and recovered
* At least 3 weeks since prior radiotherapy
* No prior gefitinib
* Prior chemotherapy or biological therapy allowed
* Prior or concurrent bisphosphonate therapy for bone metastases allowed
* No concurrent phenytoin, carbamazepine, rifampin, barbiturates, phenobarbital, or Hypericum perforatum (St. John's wort)
* No other concurrent agents specifically designed to inhibit the epidermal growth factor receptor (EGFR)
* No concurrent radiotherapy to measurable lesions

Primary outcomes:
measure: Six-month Progression-free Survival
timeFrame: From the date treatment started until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
Secondary outcomes:
measure: Number of Participants With Overall Response as Measured by RECIST Criteria
timeFrame: After 2 cycles of treatment, up to 2 years.
measure: Progression-Free Survival
timeFrame: Until disease progression, up to 5 years.
measure: Overall Survival
timeFrame: Up to 5 years.
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
Study officials:
affiliation: University of California, Davis
name: Primo N. Lara, MD
role: STUDY_CHAIR
References:
citation: Shek D, Longmate J, Quinn DI, Margolin KA, Twardowski P, Gandara DR, Frankel P, Pan CX, Lara PN Jr. A phase II trial of gefitinib and pegylated IFNalpha in previously treated renal cell carcinoma. Int J Clin Oncol. 2011 Oct;16(5):494-9. doi: 10.1007/s10147-011-0212-8. Epub 2011 Mar 23.