Low-dose IL-2 Plus IFN-alpha Immunotherapy as Adjuvant Treatment of Renal Carcinoma.

Carcinoma, Renal Cell Clinical Trial

Official title:

Adjuvant Low-dose Interleukin-2 (IL2) Plus Interferone-alpha (IFN) in Operable Renal Cell Cancer (RCC). Phase III, Randomized, Multicenter Trial of the Italian Oncology Group for Clinical Research (GOIRC).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00502034
• Other study ID #: POLAR 01
• Status: Completed
• Phase: Phase 3
• First received: July 16, 2007
• Last updated: July 9, 2013
• Start date: July 1994
• Est. completion date: June 2012

Study information

• Verified date: July 2013
• Source: Gruppo Oncologico Italiano di Ricerca Clinica
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to compare the efficacy (in terms of event-free survival and overall survival) of an adjuvant therapy with IFN-alpha plus low-dose of IL2 vs a wait-and-see program in patient with radically operated renal cell carcinoma.

Description:

For pts with non-metastatic RCC, no standard adjuvant treatment exists. Immunotherapy (IT) using IFN and/or IL2 is effective in metastatic disease setting. Low and chronically repeated doses of IL2 plus IFN induce a persistent stimulation of the immune system with no relevant toxicity.

Surgically treated RCC pts were randomized to the following arms: A) low-dose IT; B) control arm. IT consisted of a 4-week cycle of s.c. IL2 (5 days/wk, 1 million UI/sqm bid d 1,2 and 1 million UI/sqm x 1 d 3,4,5) + IFN (1,8 million UI/sqm d 3,5 of each week). Cycles were repeated every 4 months for the first 2 years and every 6 months for the remaining 3 years. Each patient received 12 cycles in 5 years. Inclusion criteria were as follows: histological diagnosis of RCC, age <75 yrs, radical or partial nephrectomy within the past 3 months, pT1 (diameter of T > 2,5 cm), T2, T3 a-b-c; pN0-pN3, M0; good cardiac and renal function and no autoimmune disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 310
• Est. completion date: June 2012
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Diagnosis histologically confirmed of renal cells carcinoma (every histotype);

• Age < 75 years

• Radical surgical removal of the tumor: total or partial nephrectomy within previous 3 months

• Patient classified as T1 (with diameter > 2,5 cm), T2, T3 a-b-c; In presence of involvement of loco-regional lymph-nodes (staging N1, N2, N3, TNM class.), metastases should have been completely removed during nephrectomy

• Absence of distant metastases;

• Written informed consent

Exclusion Criteria:

• Tumor diameter equal or less than 2,5 cm;

• Previous chemotherapy or ormonotherapy o immunotherapy;

• Renal insufficiency >3 mg/dl);

• No symptomatic arrhythmias or autoimmune disease

Study Design

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell

Intervention

Drug:
• Interferon Alfa-2a
Interferon Alfa-2a in combination with Interleukin
• Interleukin-2
Interferon Alfa-2a in combination with Interleukin

Locations

Country	Name	City	State
Italy	Ospedali Riuniti di Bergamo	Bergamo
Italy	Carpi Hospital	Carpi	Modena
Italy	Istituti Ospitalieri di Cremona	Cremona
Italy	Modena University Hospital	Modena
Italy	Parma University Hospital	Parma
Italy	Pavia University Hospital	Pavia
Italy	Ospedale "Guglielmo da Saliceto"	Piacenza
Italy	Arcispedale Santa Maria Nuova	Reggio Emilia

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Oncologico Italiano di Ricerca Clinica

Country where clinical trial is conducted

Italy, 

References & Publications (4)

Buzio C, Andrulli S, Santi R, Pavone L, Passalacqua R, Potenzoni D, Ferrozzi F, Giacosa R, Vaglio A. Long-term immunotherapy with low-dose interleukin-2 and interferon-alpha in the treatment of patients with advanced renal cell carcinoma. Cancer. 2001 Nov 1;92(9):2286-96. — View Citation

Buzio C, De Palma G, Passalacqua R, Potenzoni D, Ferrozzi F, Cattabiani MA, Manenti L, Borghetti A. Effectiveness of very low doses of immunotherapy in advanced renal cell cancer. Br J Cancer. 1997;76(4):541-4. — View Citation

Giacosa R, Santi R, Vaglio A, Pavone L, Ferrozzi F, Passalacqua R, Buzio C. "Late" regressions of metastases from renal cancer after a period of disease progression continuing the same intermittent low dose immunotherapy regimen. Acta Biomed. 2004 Aug;75(2):126-30. — View Citation

Passalacqua R, Buti S, Tomasello G, Longarini R, Brighenti M, Dalla Chiesa M. Immunotherapy options in metastatic renal cell cancer: where we are and where we are going. Expert Rev Anticancer Ther. 2006 Oct;6(10):1459-72. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence-free survival: loco-regional, adrenal, kidney and distant-metastases were the events considered for event-free survival.			No
Secondary	Tolerability, toxicity and safety.			Yes