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

• ClinicalTrials.gov Identifier: NCT00467077
• Recruitment Status: Terminated
• First Posted: April 27, 2007
• Results First Posted: March 17, 2017
• Last Update Posted: March 17, 2017
• Sponsor: California Cancer Consortium
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): California Cancer Consortium

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Kidney Cancer	Biological: PEG-interferon alfa-2b; Drug: gefitinib	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of ZD1839 (IRESSA®) and Pegylated Interferon Alfa 2b (PEG-Intron™) in Unresectable or Metastatic Renal Cell Carcinoma
• Study Start Date: September 2004
• Actual Primary Completion Date: March 2011
• Actual Study Completion Date: March 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Gefitinib and PEG-IFNa Treatment; 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; PEG-Interferon will be administered subcutaneously (sq) once weekly for 6 weeks; Drug: gefitinib; ZD1839 will be administered at a dose of 250 mg orally once daily,

Outcome Measures

Primary Outcome Measures :

1. Six-month Progression-free Survival [ Time Frame: 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 ]
   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

Secondary Outcome Measures :

1. Number of Participants With Overall Response as Measured by RECIST Criteria [ Time Frame: After 2 cycles of treatment, up to 2 years. ]
   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
2. Progression-Free Survival [ Time Frame: Until disease progression, up to 5 years. ]
   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.
3. Overall Survival [ Time Frame: Up to 5 years. ]
   Estimated using the product-limit method of Kaplan and Meier.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

City of Hope Comprehensive Cancer Center

Duarte, California, United States, 91010-3000

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States, 90089-9181

University of California Davis Cancer Center

Sacramento, California, United States, 95817

Sponsors and Collaborators

California Cancer Consortium

National Cancer Institute (NCI)

Investigators

• Study Chair: Primo N. Lara, MD; University of California, Davis

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 IFNα 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.

• Responsible Party: California Cancer Consortium
• ClinicalTrials.gov Identifier: NCT00467077
• Other Study ID Numbers: CDR0000540598; P30CA093373 ( U.S. NIH Grant/Contract ); CCC-PHII-40; ZENECA-AZ1839US/0227; UCD-200412338-4; UCD-ZD1839
• First Posted: April 27, 2007
• Results First Posted: March 17, 2017
• Last Update Posted: March 17, 2017
• Last Verified: January 2017

Keywords provided by California Cancer Consortium:

recurrent renal cell cancer; stage IV renal cell cancer; stage III renal cell cancer

Additional relevant MeSH terms:

Kidney Neoplasms; Carcinoma, Renal Cell; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Interferons; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b; Gefitinib; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Immunologic Factors; Physiological Effects of Drugs; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action