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

Phase II Trial of ZD1839 (IRESSA®) and Pegylated Interferon Alfa 2b (PEG-Intron™) in Unresectable or Metastatic Renal Cell Carcinoma

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.

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.

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