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

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).

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Renal Cell
• Intervention / Treatment: Drug: Interferon Alfa-2a; Drug: Interleukin-2

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.

• Study Type: Interventional
• Enrollment (Actual): 310
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Bergamo, Italy, 24128
    • Ospedali Riuniti di Bergamo
  • Cremona, Italy, 26100
    • Istituti Ospitalieri di Cremona
  • Modena, Italy, 41100
    • Modena University Hospital
  • Parma, Italy, 43100
    • Parma University Hospital
  • Pavia, Italy, 27100
    • Pavia University Hospital
  • Piacenza, Italy, 29100
    • Ospedale "Guglielmo Da Saliceto"
  • Reggio Emilia, Italy, 42100
    • Arcispedale Santa Maria Nuova
  • Modena
    • Carpi, Modena, Italy, 41012
      • Carpi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A-immunotherapy; Immunotherapy with interferon-alpha and interleukin	Drug: Interferon Alfa-2a; Interferon Alfa-2a in combination with Interleukin; Drug: Interleukin-2; Interferon Alfa-2a in combination with Interleukin
No Intervention: B-follow-up; Wait-and-see

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Recurrence-free survival: loco-regional, adrenal, kidney and distant-metastases were the events considered for event-free survival.

Secondary Outcome Measures

Outcome Measure
Tolerability, toxicity and safety.

Collaborators and Investigators

• Sponsor: Gruppo Oncologico Italiano di Ricerca Clinica
• Investigators: Study Chair: Rodolfo Passalacqua, Medicine, Gruppo Oncologico Italiano di Ricerca Clinica; Study Chair: Carlo Buzio, Medicine, Parma University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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. Erratum In: J Immunother. 2015 Jun;38(5):216.

Study record dates

Study Major Dates

• Study Start: July 1, 1994
• Primary Completion (Actual): April 1, 2007
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: July 16, 2007
• First Submitted That Met QC Criteria: July 16, 2007
• First Posted (Estimate): July 17, 2007

Study Record Updates

• Last Update Posted (Estimate): July 10, 2013
• Last Update Submitted That Met QC Criteria: July 9, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Carcinoma, Renal Cell; Low-dose Interleukin; Adjuvant Immunotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Interferon alpha-2; Interleukin-2
• Other Study ID Numbers: POLAR 01