Clinical trial NCT00003279: Vaccination Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer
Official title: The SILVA Study: Survival in an International Phase III Prospective Randomized LD Small Cell Lung Cancer Vaccination Study With Adjuvant BEC2 and BCG
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: limited stage small cell lung cancer
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2004-08-25
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Vaccines may help the body build an immune response to kill tumor cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of vaccination with monoclonal antibody BEC2 and BCG with that of no further therapy in treating patients who have limited-stage small cell lung cancer.

Detailed description: OBJECTIVES: I. Determine the impact of adjuvant monoclonal antibody BEC2 and BCG on survival of patients with limited stage small cell lung cancer. II. Determine the safety of this regimen in these patients. III. Determine progression-free survival and quality of life of these patients treated with this regimen.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, Karnofsky performance status (60-70% vs 80-100%), and response to first-line combined modality treatment (complete vs partial). Within 3-7 weeks after completion of prior induction chemoradiotherapy, responding patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive best supportive care and are observed until disease progression is documented. Arm II: Patients receive adjuvant monoclonal antibody BEC2 and BCG intradermally on day 1 of weeks 0, 2, 4, 6, and 10. Treatment consists of 5 vaccinations over a period of 10 to 12 weeks in the absence of unacceptable toxicity or disease progression. Quality of life is assessed at baseline, at weeks 6, 12, and 24, and then every 6 months thereafter. Patients are followed every 3 months.

PROJECTED ACCRUAL: Approximately 500 patients will be accrued for this study within 4 years.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically or cytologically proven limited stage small cell lung cancer (SCLC) Must have completed adequate first-line combined modality treatment comprising at least 4-6 courses of a 2-drug chemotherapy regimen and chest radiotherapy No evidence of disease progression or relapse Disease response (complete or partial) after treatment

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: WBC greater that 3,000/mm3 Platelet count greater than 100,000/mm3 Hepatic: AST less than 1.5 times upper limit of normal Hepatitis B negative Renal: Not specified Cardiovascular: Adequate cardiac function Other: HIV negative Not pregnant or nursing Fertile patients must use effective contraception No prior malignancy within 5 years except adequately treated nonmelanomatous skin cancer or carcinoma in situ of the cervix No history of tuberculosis No grade 3 local skin toxicity reaction (ulceration) to 5 IU or greater of PPD test No active infections requiring systemic antibiotics, antiviral, or antifungal treatments No serious unstable chronic illnesses No psychological, familial, sociological, or geographical condition that would preclude study

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior therapy with proteins of murine origin At least one month since prior immunotherapy No other concurrent immunotherapy Chemotherapy: See Disease Characteristics No concurrent chemotherapy Endocrine therapy: No concurrent chronic use of systemic corticosteroids Radiotherapy: See Disease Characteristics No concurrent radiotherapy including prophylactic cranial irradiation No prior spleen radiotherapy Surgery: No prior surgery for SCLC No prior splenectomy Other: No prior second-line therapy for SCLC At least one month since prior investigational agents No concurrent chronic use of systemic antihistamines or nonsteroidal anti-inflammatory drugs No concurrent immunosuppressive therapy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: La Jolla
country: United States
facility: Scripps Clinic and Research Foundation - La Jolla
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Denver
country: United States
facility: Colorado Permanente Medical Group, P.C.
state: Colorado
city: Bridgeport
country: United States
facility: Bridgeport Hospital
state: Connecticut
city: Greenwich
country: United States
facility: Greenwich Hospital Association
state: Connecticut
city: Hartford
country: United States
facility: St. Francis Hospital and Medical Center
state: Connecticut
city: Norwich
country: United States
facility: Norwich Cancer Center
state: Connecticut
city: Stamford
country: United States
facility: Bennett Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Veterans Affairs Medical Center - Washington, DC
state: District of Columbia
city: Hollywood
country: United States
facility: Memorial Regional Cancer Center
state: Florida
city: Miami
country: United States
facility: Mercy Hospital
state: Florida
city: Miami
country: United States
facility: Sylvester Cancer Center, University of Miami
state: Florida
city: North Miami Beach
country: United States
facility: Columbia - HCA Cancer Research Network
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Decatur
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: West Roxbury
country: United States
facility: Veterans Affairs Medical Center - West Roxbury
state: Massachusetts
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Great Falls
country: United States
facility: Benefis Healthcare
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Las Vegas
country: United States
facility: Southwest Cancer Clinic
state: Nevada
city: Reno
country: United States
facility: University of Nevada - Reno
state: Nevada
city: East Orange
country: United States
facility: Veterans Affairs Medical Center - East Orange
state: New Jersey
city: Buffalo
country: United States
facility: Veterans Affairs Medical Center - Buffalo
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Akron
country: United States
facility: Akron City Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Christ Hospital
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Oncology Inc.
state: Oklahoma
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: Charleston
country: United States
facility: Charleston Area Medical Center
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital, Sydney
state: New South Wales
city: Concord
country: Australia
facility: Repatriation General Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: Newcastle Mater Misericordiae Hospital
state: New South Wales
city: Penrith
country: Australia
facility: Nepean Hospital
state: New South Wales
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Westmead
country: Australia
facility: NSW Breast Cancer Institute
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: East Bentweigh
country: Australia
facility: Monash Medical Center
state: Victoria
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Institute
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Vienna (Wein)
country: Austria
facility: Pulmologisches Zentrum Der Stadt Wien
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Berlin
country: Germany
facility: Universitaetsklinikum Benjamin Franklin
city: Gauting, Munich (Munchen)
country: Germany
facility: Asklepios Fachkliniken Munchen- Gauting
city: Grosshansdorf
country: Germany
facility: Hospital Grosshansdorf
city: Heidelberg
country: Germany
facility: Thoraxklinik Rohrbach
city: Herne
country: Germany
facility: Marienhospital/Ruhr University Bochum
city: 's-Hertogenbosch
country: Netherlands
facility: Groot Ziekengasthuis 's-Hertogenbosch
city: Amsterdam
country: Netherlands
facility: Academisch Ziekenhuis der Vrije Universiteit
city: Harderwijk
country: Netherlands
facility: Ziekenhuis St Jansdal
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Ziekenhuis
city: Tilburg
country: Netherlands
facility: Twee Steden Ziekenhuis Vestiging Tilburg
city: Auckland
country: New Zealand
facility: Green Lane Hospital
city: Wellington
country: New Zealand
facility: Wellington Cancer Centre
city: Barakaldo, Bilbao
country: Spain
facility: Hospital de Cruces
city: Barcelona
country: Spain
facility: Hospital de la Santa Cruz I Sant Pau
city: Barcelona
country: Spain
facility: Ciudad Sanitaria Vall D'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic y Provincial de Barcelona
city: Elche
country: Spain
facility: Hospital Universitario de Elche
city: Madrid
country: Spain
facility: Hospital de la Princesa
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: San Sebastian
country: Spain
facility: Hospital Nostra Senora Aranzazu
city: Valencia
country: Spain
facility: Hospital Universitario LA FE
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital General Universitario Valencia
city: Valencia
country: Spain
facility: Hospital Arnau Vilanova
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
city: Basel
country: Switzerland
facility: University Hospital
city: Bern
country: Switzerland
facility: Inselspital, Bern
city: Chur
country: Switzerland
facility: Ratisches Kantons und Regionalspital
city: Saint Gallen
country: Switzerland
facility: Kantonsspital - Saint Gallen
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: England
Study officials:
affiliation: Free University Medical Center
name: Giuseppe Giaccone, MD, PhD
role: STUDY_CHAIR
References:
citation: Bottomley A, Debruyne C, Felip E, Millward M, Thiberville L, D'Addario G, Rome L, Zatloukal P, Coens C, Giaccone G. Symptom and quality of life results of an international randomised phase III study of adjuvant vaccination with Bec2/BCG in responding patients with limited disease small-cell lung cancer. Eur J Cancer. 2008 Oct;44(15):2178-84. doi: 10.1016/j.ejca.2008.06.036.