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

NCT ID: NCT00502034

Last Updated: 2013-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 310 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1994-07-31
• Study Completion Date: 2012-06-30

Brief 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.

Detailed 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.

Conditions

Carcinoma, Renal Cell

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A-immunotherapy

Immunotherapy with interferon-alpha and interleukin

Group Type: EXPERIMENTAL

Interferon Alfa-2a

Intervention Type: DRUG

Interferon Alfa-2a in combination with Interleukin

Interleukin-2

Intervention Type: DRUG

Interferon Alfa-2a in combination with Interleukin

B-follow-up

Wait-and-see

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Interferon Alfa-2a

Interferon Alfa-2a in combination with Interleukin

Intervention Type: DRUG

Interleukin-2

Interferon Alfa-2a in combination with Interleukin

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Oncologico Italiano di Ricerca Clinica

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rodolfo Passalacqua, Medicine

Role: STUDY_CHAIR

Gruppo Oncologico Italiano di Ricerca Clinica

Carlo Buzio, Medicine

Role: STUDY_CHAIR

Parma University

Locations

Carpi Hospital

Carpi, Modena, Italy

Ospedali Riuniti di Bergamo

Bergamo, , 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, , Italy

Countries

Italy

References

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. doi: 10.1586/14737140.6.10.1459.

Reference Type: BACKGROUND

PMID: 17069530 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15481703 (View on PubMed)

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. doi: 10.1002/1097-0142(20011101)92:93.0.co;2-i.

Reference Type: BACKGROUND

PMID: 11745283 (View on PubMed)

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. doi: 10.1038/bjc.1997.422.

Reference Type: BACKGROUND

PMID: 9275034 (View on PubMed)

Passalacqua R, Caminiti C, Buti S, Porta C, Camisa R, Braglia L, Tomasello G, Vaglio A, Labianca R, Rondini E, Sabbatini R, Nastasi G, Artioli F, Prati A, Potenzoni M, Pezzuolo D, Oliva E, Alberici F, Buzio C; POLAR-01 Trial Investigators. Adjuvant low-dose interleukin-2 (IL-2) plus interferon-alpha (IFN-alpha) in operable renal cell carcinoma (RCC): a phase III, randomized, multicentre trial of the Italian Oncology Group for Clinical Research (GOIRC). J Immunother. 2014 Nov-Dec;37(9):440-7. doi: 10.1097/CJI.0000000000000055.

Reference Type: DERIVED

PMID: 25304727 (View on PubMed)

Other Identifiers

POLAR 01

Identifier Type: -

Identifier Source: org_study_id