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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Kidney Cancer

Intervention / Treatment
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* Biological: PEG-interferon alfa-2b
* Drug: gefitinib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gefitinib and PEG-IFNa Treatment<br>Gefitinib administered at a dose of 250 mg orally once daily for 12 weeks. PEG-IFNa at 4.0 µg/kg/wk administered subcutaneously once weekly for 6 weeks (cycle repeated once for a total of 2 cycles). | Biological: PEG-interferon alfa-2b<br>* PEG-Interferon will be administered subcutaneously (sq) once weekly for 6 weeks<br>Drug: gefitinib<br>* ZD1839 will be administered at a dose of 250 mg orally once daily,<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six-month Progression-free Survival | Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Overall Response as Measured by RECIST Criteria | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response = CR + PR | After 2 cycles of treatment, up to 2 years. | 
| Progression-Free Survival | Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Until disease progression, up to 5 years. | 
| Overall Survival | Estimated using the product-limit method of Kaplan and Meier. | Up to 5 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent renal cell cancer, stage IV renal cell cancer, stage III renal cell cancer