Interleukin-2 in Treating Patients With Stage III or Stage IV Kidney Cancer

Kidney Cancer Clinical Trial

Official title:

A Randomized Controlled Phase III Adjuvant Trial of High-Dose Bolus IL-2 in Patients With High-Risk Renal Cell Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003126
• Other study ID #: 852006
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: January 2, 2017
• Start date: June 1997
• Est. completion date: August 2002

Study information

• Verified date: January 2017
• Source: Loyola University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy of post-operative high-dose bolus interleukin-2 (IL-2) in patients with high-risk renal cell carcinoma (RCC).

Description:

The primary objective of this prospective, randomized, controlled trial is to compare the disease-free and overall survival of patients with stage III or IV high-risk renal cell carcinoma (RCC) who were treated with adjuvant high-dose interleukin-2 vs observation alone.

Patients are stratified according to their disease classification and randomized to one course of IL-2 [600,000 U/kg every 8 hours on days 1 to 5 and days 15 to 19 (maximum 28 doses)] or observation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: August 2002
• Est. primary completion date: August 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

Inclusion Criteria

• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Adequate organ function as defined by a white blood cell (WBC) count of 4,000/L; a platelet count of 100,000/L; a Hemoglobin level of 10 g/dL; a serum creatinine of 1.5 mg/dL or creatinine clearance of 60 mL/min; and a direct bilirubin level of 1.5 mg/dL.

• Forced expiratory volume at 1 second more than 2.0 L or 75% of predicted for height and age from pre-enrollment pulmonary function testing.

• No history or evidence of cardiac disease on ECG

• No prior systemic treatment for RCC, but patients may have received prior locoregional radiation therapy to solitary resectable metastases, which must have undergone surgical resection before enrollment.

• No prior history of invasive malignancy in the past 5 years

• Human immunodeficiency virus (HIV) negative

• Female patients must not be pregnant or planning to become pregnant

Exclusion criteria

• Age younger than 16

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Kidney Cancer
• Kidney Neoplasms

Intervention

Drug:
• Interleukin-2
High-dose bolus interleukin-2 is a systemic therapy used to treat metastatic RCC

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Our Lady of Mercy Medical Center	Bronx	New York
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center and Beckman Research Institute, City of Hope	Duarte	California
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Summit Medical Center	Oakland	California
United States	Earle A. Chiles Research Institute at Providence Portland Medical Center	Portland	Oregon
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Loyola University	Chiron Corporation

Country where clinical trial is conducted

United States, 

References & Publications (25)

Atkins MB, Dutcher J, Weiss G, Margolin K, Clark J, Sosman J, Logan T, Aronson F, Mier J; Cytokine Working Group.. Kidney cancer: the Cytokine Working Group experience (1986-2001): part I. IL-2-based clinical trials. Med Oncol. 2001;18(3):197-207. Review. — View Citation

Atkins MB, Sparano J, Fisher RI, Weiss GR, Margolin KA, Fink KI, Rubinstein L, Louie A, Mier JW, Gucalp R, et al. Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma. J Clin Oncol. 1993 Apr;11(4):661-70. — View Citation

Belldegrun A, Webb DE, Austin HA 3rd, Steinberg SM, White DE, Linehan WM, Rosenberg SA. Effects of interleukin-2 on renal function in patients receiving immunotherapy for advanced cancer. Ann Intern Med. 1987 Jun;106(6):817-22. — View Citation

Clark JI, Atkins MB, Urba WJ, Creech S, Figlin RA, Dutcher JP, Flaherty L, Sosman JA, Logan TF, White R, Weiss GR, Redman BG, Tretter CP, McDermott D, Smith JW, Gordon MS, Margolin KA. Adjuvant high-dose bolus interleukin-2 for patients with high-risk ren — View Citation

Dutcher J, Atkins MB, Margolin K, Weiss G, Clark J, Sosman J, Logan T, Aronson F, Mier J; Cytokine Working Group.. Kidney cancer: the Cytokine Working Group experience (1986-2001): part II. Management of IL-2 toxicity and studies with other cytokines. Med Oncol. 2001;18(3):209-19. Review. — View Citation

Dutcher JP, Logan T, Gordon M, Sosman J, Weiss G, Margolin K, Plasse T, Mier J, Lotze M, Clark J, Atkins M. Phase II trial of interleukin 2, interferon alpha, and 5-fluorouracil in metastatic renal cell cancer: a cytokine working group study. Clin Cancer Res. 2000 Sep;6(9):3442-50. — View Citation

Finney R. The value of radiotherapy in the treatment of hypernephroma--a clinical trial. Br J Urol. 1973 Jun;45(3):258-69. — View Citation

Fisher RI, Rosenberg SA, Fyfe G. Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am. 2000 Feb;6 Suppl 1:S55-7. — View Citation

Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995 Mar;13(3):688-96. — View Citation

Guinan P, Sobin LH, Algaba F, Badellino F, Kameyama S, MacLennan G, Novick A. TNM staging of renal cell carcinoma: Workgroup No. 3. Union International Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer. 1997 Sep 1;80(5):992-3. — View Citation

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Margolin KA, Rayner AA, Hawkins MJ, Atkins MB, Dutcher JP, Fisher RI, Weiss GR, Doroshow JH, Jaffe HS, Roper M, et al. Interleukin-2 and lymphokine-activated killer cell therapy of solid tumors: analysis of toxicity and management guidelines. J Clin Oncol. 1989 Apr;7(4):486-98. — View Citation

McDermott DF, Regan MM, Clark JI, Flaherty LE, Weiss GR, Logan TF, Kirkwood JM, Gordon MS, Sosman JA, Ernstoff MS, Tretter CP, Urba WJ, Smith JW, Margolin KA, Mier JW, Gollob JA, Dutcher JP, Atkins MB. Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol. 2005 Jan 1;23(1):133-41. Erratum in: J Clin Oncol. 2005 Apr 20;23(12):2877. — View Citation

Messing EM, Manola J, Wilding G, Propert K, Fleischmann J, Crawford ED, Pontes JE, Hahn R, Trump D; Eastern Cooperative Oncology Group/Intergroup trial.. Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial. J Clin Oncol. 2003 Apr 1;21(7):1214-22. — View Citation

Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol. 1999 Aug;17(8):2530-40. — View Citation

Naito S, Kumazawa J, Omoto T, Iguchi A, Sagiyama K, Osada Y, Hiratsuka Y. Postoperative UFT adjuvant and the risk factors for recurrence in renal cell carcinoma: a long-term follow-up study. Kyushu University Urological Oncology Group. Int J Urol. 1997 Jan;4(1):8-12. — View Citation

Negrier S, Escudier B, Lasset C, Douillard JY, Savary J, Chevreau C, Ravaud A, Mercatello A, Peny J, Mousseau M, Philip T, Tursz T. Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma. Groupe Français d'Immunothérapie. N Engl J Med. 1998 Apr 30;338(18):1272-8. — View Citation

Pizzocaro G, Piva L, Colavita M, Ferri S, Artusi R, Boracchi P, Parmiani G, Marubini E. Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study. J Clin Oncol. 2001 Jan 15;19(2):425-31. — View Citation

Poster DS, Bruno S, Penta JS, Pinna K, Vilk P, Macdonald JS. Current status of chemotherapy, hormonal therapy, and immunotherapy in the treatment of renal cell carcinoma. Am J Clin Oncol. 1982 Feb;5(1):53-60. — View Citation

Robson CJ, Churchill BM, Anderson W. The Results of Radical Nephrectomy for Renal Cell Carcinoma. J Urol. 2016 Dec 21. pii: S0022-5347(16)31648-2. doi: 10.1016/j.juro.2016.10.095. [Epub ahead of print] — View Citation

Rosenberg SA, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA. 1994 Mar 23-30;271(12):907-13. — View Citation

Skinner DG, Colvin RB, Vermillion CD, Pfister RC, Leadbetter WF. Diagnosis and management of renal cell carcinoma. A clinical and pathologic study of 309 cases. Cancer. 1971 Nov;28(5):1165-77. — View Citation

Upton MP, Parker RA, Youmans A, McDermott DF, Atkins MB. Histologic predictors of renal cell carcinoma response to interleukin-2-based therapy. J Immunother. 2005 Sep-Oct;28(5):488-95. — View Citation

Weiss GR, Margolin KA, Aronson FR, Sznol M, Atkins MB, Dutcher JP, Gaynor ER, Boldt DH, Doroshow JH, Bar MH, et al. A randomized phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma. J Clin Oncol. 1992 Feb;10(2):275-81. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease free survival	Disease free survival will be compared between the two cohorts (i.e., IL-2 versus Observation). Time will be calculated as the difference in months from date of treatment to date of death or recurrence (whichever occurs first). Patients remaining disease-free will be censored at the date of last follow-up.	60 months	No
Secondary	Overall survival	Overall survival will be compared between the two cohorts (i.e., IL-2 versus Observation). Time will be calculated as the difference in months from date of treatment to date of death. Living patients will be censored at the date of last follow-up.	60 months	No