Survival in a Randomized Phase III Trial in Patients With Limited Disease (LD) Small Cell Lung Cancer Vaccinated With Adjuvant BEC2 and BCG

The SILVA Study: Survival in an International Phase III Prospective Randomized LD Small Cell Lung Cancer Vaccination Study With Adjuvant BEC2 and BCG

This trial is designed to test the impact of adjuvant BEC2 (2.5 mg)/BCG vaccination on survival in patients with LD Small Cell Lung Cancer (SCLC). Patients will be stratified by institution, KPS (60 - 70% vs 80 - 100%), and response to first line combined modality therapy (CR vs PR) that consisted of at least a 2 drug regimen (4 - 6 cycles) and a chest radiotherapy regimen. Patients will be randomized to one of two treatment arms: standard arm (Observational cohort) or best supportive care, or the treatment arm (5 intradermal vaccinations of BEC2 (2.5 mg) + BCG given on day 1 of weeks 0, 2, 4, 6, and 10.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Small Cell Lung
• Intervention / Treatment: Biological: BEC2 Vaccine

• Study Type: Interventional
• Enrollment (Actual): 515
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histo-cytologically proven SCLC
• Limited disease at diagnosis
• Age greater than or equal to 18
• Patients with a clinical response of CR or PR to first line combined modality therapy
• KPS greater than or equal to 60
• Adequate bone marrow, liver and heart functions
• Written informed Consent

Exclusion Criteria:

• Prior surgical treatment for SCLC
• History of tuberculosis
• NCIC CTG grade 3 local skin toxicity reaction (ulceration) to > IU PPD test > 5 IU
• HIV positive
• Splenectomy or spleen radiation therapy in medical history
• Prior therapy to proteins of murine origin
• Any second line therapy for SCLC
• Investigational agent or immune therapy within 4 weeks prior to study randomization
• Severe active infections
• Active infections requiring systemic antibiotics, antiviral, or antifungal treatments
• Serious unstable chronic illness
• The use of systemic anti-histamines, NSAID or systemic corticosteroids
• Any previous malignancy except adequately treated CIS of the cervix or non melanoma skin cancer or if previous malignancy was more than 5 years prior and there are no signs of recurrence
• Pregnancy or breast feeding or absence of adequate contraception for fertile patients
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before randomization in the trial.

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
No Intervention: 1; Best supportive care, but no cancer specific therapy (cytotoxic, radiation or other tumor reductive therapy) can be given until documented progression of disease.
Experimental: 2; Treatment will consist of 5 vaccinations (each consisting of 8 single intradermal injections) over a period of 10 to 12 weeks unless one of the following occur: intolerable toxicity precluding further treatment progression of disease; patient refusal; occurrence of pregnancy	Biological: BEC2 Vaccine; 5 vaccinations of BEC2 (2.5 mg) + BCG given day 1 of weeks 0,2,4,6 & 10.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	6 monthly basis until progression of disease

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	6 monthly basis until progression of disease
Safety	6 monthly basis until progression of disease
Quality of Life	6 monthly basis until progression of disease
Health Economics Aspects	6 monthly basis until progression of disease

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Memorial Sloan Kettering Cancer Center; Merck KGaA, Darmstadt, Germany; US Department of Veterans Affairs; Spanish Lung Cancer Group; Groupe Francais De Pneumo-Cancerologie; EORTC Lung Cancer Cooperative Group; Schweizerische Arbeitsgruppe fuer angewandte Krebsforschung (SAKK); Independent centers (Australia, New Zealand, Europe, USA)

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start: September 1, 1998
• Primary Completion (Actual): October 1, 2002
• Study Completion (Actual): October 1, 2002

Study Registration Dates

• First Submitted: May 20, 2002
• First Submitted That Met QC Criteria: May 20, 2002
• First Posted (Estimate): May 21, 2002

Study Record Updates

• Last Update Posted (Estimate): April 8, 2010
• Last Update Submitted That Met QC Criteria: April 7, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: LD Small Cell Lung Cancer; BEC2, vaccine; adjuvant, monoclonal antibody; LD Small Cell Lung Cancer (VA Classification, Zelen, 1973)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Carcinoma, Small Cell
• Other Study ID Numbers: SILVA EORTC 08971