Non-small Cell Lung CancerPhase 3STARTNCT00409188
Cancer Vaccine Study for Unresectable Stage III Non-small Cell Lung Cancer (START)
A Phase 3 study testing Tecemotide (L-BLP25) and Single low dose cyclophosphamide in people with Non-small Cell Lung Cancer, run by EMD Serono at 290 sites in 33 countries.
Trial summary
The purpose of this study is to determine whether the cancer vaccine tecemotide (L-BLP25) in addition to best supportive care is effective in prolonging the lives of subjects with unresectable stage III non-small cell lung cancer, compared to best supportive care alone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Tecemotide (L-BLP25) and Single low dose cyclophosphamide
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,513 participants
- Where
- 290 sitesin 33 countries
- Study dates
- Jan 2007to Apr 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically documented unresectable stage III non-small cell lung cancer (NSCLC)
- Documented stable disease or objective response, according to Response Evaluation Criteria in Solid Tumors (RECIST), after primary chemoradiotherapy (either sequential or concomitant) for unresectable stage III disease, within 4 weeks (28 days) prior to randomization
- Receipt of concomitant or sequential chemoradiotherapy, consisting of a minimum of two cycles of platinum-based chemotherapy and a minimum radiation dose of >=50 Gray (Gy). Subjects must have completed the primary thoracic chemo-radiotherapy at least four weeks (28 days) and no later than 12 weeks (84 days) prior to randomization. Subjects who received prophylactic brain irradiation as part of primary chemo-radiotherapy are eligible
- Geographically accessible for ongoing follow-up, and committed to comply with the designated visits
- An Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- A platelet count > 140 x 10^9/Liter; white blood cells (WBC) > 2.5 x 10^9/Liter and hemoglobin > 90 gram per liter (g/L)
Who cannot join
- Pre-Therapies:
- Undergone lung cancer specific therapy (including surgery) other than primary chemo-radiotherapy
- Receipt of immunotherapy (e.g. interferons, tumor necrosis factor [TNF], interleukins, or biological response modifiers [granulocyte macrophage colony stimulating factor {GM-CSF}, granulocyte colony stimulating factor {G-CSF}, macrophage-colony stimulating factor {M-CSF}], monoclonal antibodies) within 4 weeks (28 days) prior to randomization
- Receipt of investigational systemic drugs (including off-label use of approved products) within 4 weeks (28 days) prior to randomization
- Disease Status:
- Metastatic disease
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- Malignant pleural effusion at initial diagnosis and/or at study entry
- Past or current history of neoplasm other than lung carcinoma, except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix or other cancer curatively treated and with no evidence of disease for at least 5 years
- Autoimmune disease
- A recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have hereditary or congenital immunodeficiencies
- Any preexisting medical condition requiring chronic steroid or immunosuppressive therapy (steroids for the treatment of radiation pneumonitis are allowed)
- Known Hepatitis B and/or C
- Physiological Functions:
- Clinically significant hepatic dysfunction
- Clinically significant renal dysfunction
- Clinically significant cardiac disease
- Splenectomy
- Infectious process that in the opinion of the investigator could compromise the subject's ability to mount an immune response
- Standard Safety:
- Pregnant or breast-feeding women, women of childbearing potential, unless using effective contraception as determined by the investigator
- Known drug abuse/alcohol abuse
- Legal incapacity or limited legal capacity
Trial locations and contacts
290 sites in 33 countries.
290 sites in 33 countries
United States49 sites
Pacific Cancer Medical Center
Anaheim, California, 92801
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
University of Maryland, Marlene and Steward Greenbaum Cancer Center
Baltimore, Maryland
Deaconess Billings Clinic
Billings, Montana, 59101
Pasco Hernando Oncology Associates P.A
Brooksville, Florida, 34613
Lahey Clinic
Burlington, Massachusetts
Gabrail Cancer Center
Canton, Ohio, 44718
Southern Illinois Hematology/Oncology
Centralia, Illinois, 62801
Univ. of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Carolinas Hematology-Oncology
Charlotte, North Carolina, 28203
Rush University Medical Center
Chicago, Illinois, 60612
University Hospitals of Cleveland
Cleveland, Ohio, 44106
Center for Oncology Research
Dallas, Texas, 75230
University of Colorado Cancer Center
Denver, Colorado, 80045
Fairfax-Northern Virginia Hematology Oncology, PC
Fairfax, Virginia, 22031
Saint Edward Mercy Medical Center
Fort Smith, Arkansas, 72901
John Peter Smith Center for Cancer Care
Fort Worth, Texas, 76104
The Center for Cancer and Blood Disorders
Fort Worth, Texas, 76104
The Jones Clinic, PC
Germantown, Tennessee, 38138
Glendale Adventist Medical Center
Glendale, California, 91206
Big Sky Oncology, Sletten Cancer Institute
Great Falls, Montana, 59405
Nebraska Cancer Care, LLC
Hastings, Nebraska, 68901
Kentucky Cancer Center
Hazard, Kentucky, 41701
Leonard J. Chabert Medical Center
Houma, Louisiana
Joliet Oncology-Hematology Associates, Ltd.
Joliet, Illinois, 60435
Southeast Nebraska Cancer Center
Lincoln, Nebraska, 68510
Norris Cancer Hospital
Los Angeles, California, 90033
Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute
Los Angeles, California, 90048
Hematology and Oncology Specialists, LLC
Metarie, Louisiana, 70006
University of Miami, Sylvester Comprehensive Cancer Center
Miami, Florida
Signal Point Clinical Research Center, LLC
Middletown, Ohio, 45042
University of Minnesota Physicians, Masonic Cancer Center
Minneapolis, Minnesota
Clinical Trials and Research Associates, Inc.
Montebello, California, 90640
Pasco Hernando Oncology Associates, PA
New Port Richey, Florida, 34652
St. Vincents Comprehensive Cancer Center
New York, New York, 10011
Hematology Oncology Associates of Rockland
Nyack, New York, 10960
Florida Hospital Memorial System
Ormond Beach, Florida, 32174
Univ. of Pennsylvania Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Providence Portland Medical Center
Portland, Oregon, 97213
Desert Hematology Oncology Medical Group, Inc
Rancho Mirage, California
Oncology Care Associates
Saint Joseph, Michigan, 49085
Cancer Therapy & Research Center, Institute for Drug Development
San Antonio, Texas, 78229
Saint Louis University Cance Center
St Louis, Missouri
Stockton Hematology Oncology Medical Group, Inc.
Stockton, California, 95204
Southwestern Regional Medical Center
Tulsa, Oklahoma, 74133
Southwestern Regional Medical Center
Tulsa, Oklahoma
Wheeling Hospital
Wheeling, West Virginia, 26003
Hanover Medical Specialts PA
Wilmington, North Carolina, 28401
Germany24 sites
Research Site
Berlin
Research Site
Cologne
Research Site
Coswig
Research Site
Essen, North Rhine-Westphalia
Research Site
Essen
Research Site
Frankfurt am Main
Research Site
Freiburg im Breisgau
Research Site
Gauting
Research Site
Großhansdorf
Research Site
Hamburg
Reseach Site
Heidelberg
Research Site
Hemer, North Rhine-Westphalia
Research Site
Homburg, Saarland
Research Site
Kassel
Research Site
Kiel
Research Site
Leipzig
Research Site
Magdeburg
Research Site
Mainz, Rhineland-Palatinate
Research Site
Mainz
Research Site
Minden
Research Site
München
Research Site
Mutzschen
Research Site
Oldenburg
Research Site
Rostock
Canada17 sites
Tom Baker Cancer Center
Calgary, Alberta
Cross Cancer Institue
Edmonton, Alberta
Capital District Health Authority
Halifax, Nova Scotia
Juravinski Cancer Center
Hamilton, Ontario
Hopital Notre Dame
Montreal, Quebec
Jewish General Hospital
Montreal, Quebec
Niagara Health System
Saint Catharines, Ontario
Hopital Laval
Sainte-Foy, Quebec
Frazer Valley Cancer Center
Surrey, British Columbia
Cape Breton Districk Health Authority Cancer Care
Sydney, Nova Scotia
Thunder Bay Regional Health Science Center Northwestern Ontario Regional Center
Thunder Bay, Ontario
Mount Sinai Hospital
Toronto, Ontario
Princess Margaret Hospital
Toronto, Ontario
British Columbia Cancer Agency
Vancouver, British Columbia
Vancouver Island Cancer Center
Victoria, British Columbia
Windsor Regional Cancer Center
Windsor, Ontario
Cancer Care Manitoba
Winnipeg, Manitoba
Italy17 sites
Research Site
Avelino
Research Site
Bologna
Research Site
Candiolo, Torino
Research Site
Carpi
Research Site
Chieti
Research Site
Forlì
Research Site
Genova, Genova
Research Site
Meldola
Research Site
Milan
Research Site
Naples
Research Site
Orbassano-Torino
Research Site
Palermo, Palermo
Research Site
Parma
Research Site
Rome
Research Site
Rozzano-Milano
Research Site
Sassari
Research Site
Trento
Brazil15 sites
Hospital LifeCenter
Belo Horizonte, Minas Gerais
Centro de Oncologia de Campinas - OCC
Campinas, São Paulo
Associacao Hospital de Caridade Ijui
Ijuí, Rio Grande do Sul
Fundacao Hospital Amaral Carvalho
Jaú, São Paulo
Research Site
Ondina-Salvdor
Hospital Nossa Senhora da Conceicao, Centro de Pesquisas Medicas e Ensaios Clinicos
Porto Alegre, Rio Grande Do Sol
Hospital de Clinicas de Porto Alegre, Dept. de Endocrinologia
Porto Alegre, Rio Grande do Sul
Hospital Sao Lucas-Pucrs
Porto Alegre, Rio Grande do Sul
Research Site
Porto Algre, Rio Grande do Sul
Instituto Nacional do Cancer - INCA
Rio de Janeriro
Nugieo de Oncologia da Bahia
Salvador, Estado de Bahia
Hospital das Clinicas da Faculdade de Medinina de Univeridade
São Paulo, De Ao Paulo
Instituto do Cancer Arnaldo Vieira de Caralho-Onco-pneumonia
São Paulo, São Paulo
Santa Casa de Misericordia De Sao Paulo
São Paulo, São Paulo
Instituto de Oncologia de Sorocaba
Sorocaba, São Paulo
Poland15 sites
Research Site
Bialystok
Research Site
Bydgoszcz
Research Site
Bytom
Research Site
Gdynia
Research Site
Krakow
Genova
Lodz
Research Site
Olsztyn
Research Site
Otwock
Research Site
Poznan
Research Site
Torun
Research Site
Warsaw, Masovian Voivodeship
Genova
Warsaw
Research Site
Warsaw
Research Site
Wroclaw
Research Site
Zabrze
France13 sites
Research Site
Besançon, Franche-Comte
Research Site
Beuvry
Research Site
Brest
Research Site
Caen
Research Site
Chauny
Research Site
Marseille
Research Site
Nancy
Research Site
Nantes-Saint Herblain
Research Site
Paris
Research Site
Perpignan
Research Site
Pierre-Bénite, Auvergne-Rhône-Alpes
Research Site
Poitiers
Research Site
Strasbourg
United Kingdom13 sites
Research Site
Cornwall
Research Site
Edinburgh
Research Site
Glasgow
Research Site
Guildford
Research Site
Inverness
Research Site
Leeds
Research Site
Leicester
Research Site
London
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Manchester
Research Site
Metropolitan Borough of Wirral
Research Site
Southampton
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Surrey
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Torquay
Spain12 sites
Research Site
A Coruña
Research Site
Alicante
Research Site
Barakaldo, Bilbao
Research Site
Barcelona
Research Site
Burgos
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Donostia / San Sebastian, Guipuzcoa
Research Site
Girona
Research Site
Jaén, Jaen
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Lugo
Research Site
Madrid
Research Site
Málaga
Research Site
Mataró, Barcelona
Russia11 sites
Research Site
Barnaul
Genova
Chelaybinsk
Research Site
Ivanovo
Reseaerch Site
Kazan', Tatarstan Republic
Research Site
Kazan'
Research Site
Moscow
Research Site
Obninsk
Research Site
Saint Petersburg
Research Site
Tomsk
Research Site
Voronezh
Research Site
Yaroslavl, Yaroslavlr
Argentina9 sites
Hospital Italiano Regional del Sur
Bahía Blanca, Buenos Aires
Centro de Educacion Medica e Investigaciones Clinicas "Norberto Quirno" (CEMIC)
Buenos Aires
Instituto Especializado Alexander Fleming
Buenos Aires
Sociedad Intaliana de Beneficencia en Buenos Aires, Hospital Italiano
Buenos Aires
Paliar
Capital, Buenos Aires, Buenos Aires
Clinica Universitaria Reina Fabiola
Córdoba
Centro Oncologico de Roario
Rosario, Santa Fe Province
Corporacion Medica General San Martin
San Martín, Buenos Aires
Research Site
Tandil
Israel8 sites
Research Site
Beersheba
Research Site
Haifa
Research Site
Jerusalem
Research Site
Kfar Saba
Research Site
Petah Tikva
Research Site
Tel Aviv
Research Site
Tel HaShomer, Tel Avir
Research Site
Tsrifin
Australia7 sites
Research Site
Bankstown, NSW
Research Site
Camperdown
Research Site
Heidelberg
Research Site
Kingswood
Research Site
Nedlands, Western Australia
Research Site
Saint Leonards
Research Site
Woolloongabba
Austria7 sites
Research Site
Graz, Styria
Research Site
Inssbruck
Research Site
Linz, Upper Austria
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Salzburg
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Vienna
Research Site
Wein, Venna
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Wels
Belgium6 sites
Research Site
Brasschaat
Research Site
Brussels
Research Site
Haine-Saint-Paul
Research Site
Leuven
Research Site
Liège
Research Site
Mechelen
Greece6 sites
Research Site
Athens, Attica
Research Site
Athens
Research Site
Chidari, Athens
Research Site
Heraklion
Research Site
Marousi, Athens
Research Site
Thessaloniki, Nea Efkarpia
Netherlands6 sites
Research Site
Amsterdam, North Holland
Research Site
Amsterdam
Research Site
Eindhoven
Research Site
Hoofdrop
Research Site
Tilburg
Research Site
Zwolle
Romania6 sites
Research Site
Bucharest
Research Site
Cluj-Napoca
Research Site
Iași
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Sibiu
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Suceava
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Timișoara
Sweden6 sites
Research Site
Gävle
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Gothenburg
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Lund
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Stockholm
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Umeå
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Uppsala
India5 sites
Research Site
Chennai
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Hyderabad
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Mumbai
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New Delhi
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Vellore
Taiwan5 sites
Research Site
Kaohsiung City
Research Site
Taichung
Research Site
Tainan
Research Site
Taipei
Research Site
Taoyuan
Czechia4 sites
Research Site
Hradec Králové
Research Site
Ostrava-Poruba
Research Site
Prague
Research Site
Ústí nad Labem
Hungary4 sites
Research Site
Budapest
Research Site
Mátraháza
Research Site
Nyíregyháza
Research Site
Tatabayana
Portugal4 sites
Genova
Coimbra
Genova
Lisbon
Genova
Porto
Genova
Santa Maria de Feira
Mexico3 sites
Centro Oncologico de Chihuahua
Chihuahua City, Chihuahua
Instituto Nacional de Cancerologia (INCAN)
Mexico City
Consultorio del
Morelia, Michoacán
Slovakia3 sites
Research Site
Bratislava
Research Site
Košice
Research Site
Nitra
South Korea3 sites
Research Site
Goyang-si, Gyeonggi-do
Research Site
Seoul, Gyeonggi-do
Research Site
Seoul
Switzerland3 sites
Research Site
Basel
Research Site
Geneva
Research Site
Winterthur
Hong Kong2 sites
Research Site
Hong Kong
Research Site
Shatin, New Territories
About this study
Official title: A Multi-center Phase III Randomized, Double-blind Placebo-controlled Study of the Cancer Vaccine Stimuvax® (L-BLP25 or BLP25 Liposome Vaccine) in Non-small Cell Lung Cancer (NSCLC) Subjects With Unresectable Stage III Disease.
The purpose of this study is to determine whether the cancer vaccine tecemotide (L-BLP25) in addition to best supportive care is effective in prolonging the lives of subjects with unresectable stage III non-small cell lung cancer, compared to best supportive care alone.
A local ancillary (sub) study in European centers will evaluate the immune response in peripheral blood after tecemotide (L-BLP25) or placebo vaccination.
Read the detailed description
Ancillary Trial: An exploratory investigation of immune response in peripheral blood after tecemotide (L-BLP25) or placebo vaccination.
The ancillary study is a sub-study within START. This is an exploratory investigation of the immune response in peripheral blood after tecemotide (L-BLP25) or placebo vaccination. The main objective is to evaluate whether administration of single-shot, low-dose cyclophosphamide followed by tecemotide (L-BLP25) vaccinations induces specific immune response in peripheral blood to BLP25 (the mucinous glycoprotein 1 [MUC1] antigen) as well as a modulation of cellular and soluble components of the immune response in subjects with unresectable stage III NSCLC.
Twenty-five of the European START sites will participate in the ancillary study.
Sample size: up to 60 to 80 subjects
All inclusion criteria specified in the START clinical trial protocol except for hemoglobin >= 100 gram/Liter (g/L)
All exclusion criteria are the same as specified in the START clinical trial protocol
Schedule of events: Blood samples will be taken at baseline, visit week 4, 8 13 and 25 (80 milliliter (mL) whole blood each)
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Tecemotide (L-BLP25), Single low dose cyclophosphamide, Placebo
- Keywords
- Non-Small Cell Lung Carcinoma;, stage III;, unresectable;, vaccine; Tecemotide; L-BLP25;, Cyclophosphamide;, placebo controlled;, randomized;, double blind;, immunotherapy;
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tecemotide (L-BLP25)Biological
After receiving cyclophosphamide, participants will receive 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance vaccinations with 806 mcg of tecemotide (L-BLP25) at 6-week intervals, commencing at Week 13, until disease progression is documented.
Single low dose cyclophosphamideDrug
A single intravenous infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg) of cyclophosphamide will be given 3 days before first tecemotide (L-BLP25) vaccination.
PlaceboDrug
A single infusion (IV) of 0.9% Saline solution instead of cyclophosphamide but in the same calculated dose will be given three days before first placebo vaccination. Subjects will then receive eight consecutive weekly subcutaneous vaccinations with placebo at weeks 0; 1; 2; 3; 4; 5; 6 and 7 followed by maintenance placebo vaccinations at 6-week intervals, commencing at week 13, until disease progression is documented.
| Study group | Role | What they receive |
|---|---|---|
| Tecemotide (L-BLP25) | Experimental | Not described Receives: Biological: Tecemotide (L-BLP25); Drug: Single low dose cyclophosphamide |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Overall survival time was defined as the time from randomization to death. Participants without events were censored at the last date they were known to be alive or the clinical cut-off date, whatever was earlier.
Measured: Up to 66 months
Secondary outcomes (4)
Time To Symptom Progression (TTSP) as Measured by the Lung Cancer Symptom Scale (LCSS)
Time to symptom progression (TTSP) was measured by LCSS. Symptomatic progression was defined as an increase (worsening) of the Average Symptomatic Burden Index (ASBI that is, the mean of the six major lung cancer specific symptom scores of the LCSS patient scale - ranging from 0 to 100 where higher score indicates worst outcome). Worsening was defined as a 10% increase in the scale breadth from the baseline score. TTSP is defined as the time from randomization to worsening in ASBI. Participants without event are censored at the date of the last LCSS assessment.
Measured: Up to 66 months
Time To Progression (TTP)
Time from randomization to disease progression. Disease progression was defined based on Response Evaluation Criteria in Solid Tumors Version 1.0 [RECIST v1.0]) as at least a 20% increase in the sum of the longest diameter of target lesions from nadir, or the appearance of one or more new lesions.
Measured: Up to 66 months
One-, Two- and Three-year Survival Rate
The percentages of participants who were alive at 1, 2, and 3 years were calculated as a cumulative percentage by Kaplan-Meier survival analysis approach.
Measured: Years 1, 2, and 3
Number of Participants With Treatment Emergent Adverse Events and Injection Site Reactions
Treatment -emergent adverse events were defined as those with onset or worsening occurring at or after the first dosing day of study medication and up to 42 days after the last administration of any study drug or the clinical cut-off date. Injection site reactions were reported as assessed by the Investigator.
Measured: From first dose up to 42 days after the last dose of the trial treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2006 (estimated)
- Study startJan 2007
- Primary completionApr 2012
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,513 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00409188
- Sponsor's protocol ID
- EMR 63325-001
- Acronym
- START
- Status last verified
- Oct 2015
- First submitted
- 7 Dec 2006
- Last updated
- 20 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Butts C, Socinski MA, Mitchell P, Thatcher N, Havel L, Krzakowski M, Nawrocki S, Ciuleanu TE, Bosquée L, Trigo JM, Spira A, Tremblay L, Nyman J, Ramlau R, Helwig C, Falk MH, Shepherd FA. START: A phase III study of L-BLP25 cancer immunotherapy for unresectable stage III non-small cell lung cancer. American Society of Clinical Oncology - 49th Annual Meeting. 2013; Abstr No. 7500.
Shepherd FA, Socinski MA, Mitchell P, Thatcher N, Havel L, Krzakowski M, Nawrocki S, Helwig C, Schroeder A, Butts C. Updated analysis and secondary endpoints with L-BLP25 in unresectable stage III non-small cell lung cancer in the phase III START study. European Society for Medical Oncology 38th Congress - ECCO 17, ESMO 38, ESTRO 32. 2013. Abstr No. 3419.
Mitchell P, Butts C, Socinski M, Thatcher N, Wichardt-Johansson G, Ellis P, Gladkov O, Pereira J, Eberhardt W, Horwood K, Szczesna A, Helwig C, Schröder A, Shepherd F. Tecemotide (L-BLP25) in unresectable stage III non-small cell lung cancer in the phase III START study: Further endpoint and exploratory biomarker results. World Conference on Lung Cancer - 15th. 2013; Abstr. No. 2779.
Thatcher N, Shepherd FA, Mitchell P, Socinski MA, Paredes A, Lambrechts M, Thomas M, Kollmeier J, Zemanová M, Sadjadian P, Peylan-Ramu N, Helwig C, Schröder A, Butts C. Geographic differences in the combined-modality treatment of stage III unresectable non-small cell lung cancer: Results from a global phase III trial of tecemotide (L-BLP25). World Conference on Lung Cancer - 15th. 2013; Abstr. No. 2712.
Socinski M, Butts C, Mitchell P, Thatcher N, Scagliotti G, Robinet G, Martin C, Zukin M, Ragulin Y, Bonomi P, Yang CH, Regnault A, Helwig C, de Nigris E, Shepherd F. Exploration of patient health status as measured by the generic preference-based questionnaire EQ-5D alongside the START trial of tecemotide in non-small cell lung cancer. World Conference on Lung Cancer - 15th. 2013; Abstr. No. 2744.
Butts C, Socinski MA, Mitchell PL, Thatcher N, Havel L, Krzakowski M, Nawrocki S, Ciuleanu TE, Bosquee L, Trigo JM, Spira A, Tremblay L, Nyman J, Ramlau R, Wickart-Johansson G, Ellis P, Gladkov O, Pereira JR, Eberhardt WE, Helwig C, Schroder A, Shepherd FA; START trial team. Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Jan;15(1):59-68. doi: 10.1016/S1470-2045(13)70510-2. Epub 2013 Dec 9.
PubMed 24331154DeGregorio M, Soe L, Wolf M. Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small cell lung cancer (START): a randomized, double-blind, phase III trial. J Thorac Dis. 2014 Jun;6(6):571-3. doi: 10.3978/j.issn.2072-1439.2014.05.15. No abstract available.
PubMed 24976972Zhu J, Yuan Y, Wan X, Yin D, Li R, Chen W, Suo C, Song H. Immunotherapy (excluding checkpoint inhibitors) for stage I to III non-small cell lung cancer treated with surgery or radiotherapy with curative intent. Cochrane Database Syst Rev. 2021 Dec 6;12(12):CD011300. doi: 10.1002/14651858.CD011300.pub3.
PubMed 34870327Mitchell P, Thatcher N, Socinski MA, Wasilewska-Tesluk E, Horwood K, Szczesna A, Martin C, Ragulin Y, Zukin M, Helwig C, Falk M, Butts C, Shepherd FA. Tecemotide in unresectable stage III non-small-cell lung cancer in the phase III START study: updated overall survival and biomarker analyses. Ann Oncol. 2015 Jun;26(6):1134-1142. doi: 10.1093/annonc/mdv104. Epub 2015 Feb 26.
PubMed 25722382
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center Phase III Randomized, Double-blind Placebo-controlled Study of the Cancer Vaccine Stimuvax® (L-BLP25 or BLP25 Liposome Vaccine) in Non-small Cell Lung Cancer (NSCLC) Subjects With Unresectable Stage III Disease.
- ClinicalTrials.gov ID
- NCT00409188
- Acronym / sponsor ID
- START / EMR 63325-001
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- Non-Small Cell Lung Carcinoma;, stage III;, unresectable;, vaccine; Tecemotide; L-BLP25;, Cyclophosphamide;, placebo controlled;, randomized;, double blind;
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,513 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- Jan 2007
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 8 Dec 2006 (estimated)
- Results
- Posted 20 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether the cancer vaccine tecemotide (L-BLP25) in addition to best supportive care is effective in prolonging the lives of subjects with unresectable stage III non-small cell lung cancer, compared to best supportive care alone.
A local ancillary (sub) study in European centers will evaluate the immune response in peripheral blood after tecemotide (L-BLP25) or placebo vaccination.
Detailed description
Ancillary Trial: An exploratory investigation of immune response in peripheral blood after tecemotide (L-BLP25) or placebo vaccination.
The ancillary study is a sub-study within START. This is an exploratory investigation of the immune response in peripheral blood after tecemotide (L-BLP25) or placebo vaccination. The main objective is to evaluate whether administration of single-shot, low-dose cyclophosphamide followed by tecemotide (L-BLP25) vaccinations induces specific immune response in peripheral blood to BLP25 (the mucinous glycoprotein 1 [MUC1] antigen) as well as a modulation of cellular and soluble components of the immune response in subjects with unresectable stage III NSCLC.
Twenty-five of the European START sites will participate in the ancillary study.
Sample size: up to 60 to 80 subjects
All inclusion criteria specified in the START clinical trial protocol except for hemoglobin >= 100 gram/Liter (g/L)
All exclusion criteria are the same as specified in the START clinical trial protocol
Schedule of events: Blood samples will be taken at baseline, visit week 4, 8 13 and 25 (80 milliliter (mL) whole blood each)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tecemotide (L-BLP25) | Experimental | Biological: Tecemotide (L-BLP25), Drug: Single low dose cyclophosphamide |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically or cytologically documented unresectable stage III non-small cell lung cancer (NSCLC)
- Documented stable disease or objective response, according to Response Evaluation Criteria in Solid Tumors (RECIST), after primary chemoradiotherapy (either sequential or concomitant) for unresectable stage III disease, within 4 weeks (28 days) prior to randomization
- Receipt of concomitant or sequential chemoradiotherapy, consisting of a minimum of two cycles of platinum-based chemotherapy and a minimum radiation dose of >=50 Gray (Gy). Subjects must have completed the primary thoracic chemo-radiotherapy at least four weeks (28 days) and no later than 12 weeks (84 days) prior to randomization. Subjects who received prophylactic brain irradiation as part of primary chemo-radiotherapy are eligible
- Geographically accessible for ongoing follow-up, and committed to comply with the designated visits
- An Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Key exclusion criteria (22 listed)
- Undergone lung cancer specific therapy (including surgery) other than primary chemo-radiotherapy
- Receipt of immunotherapy (e.g. interferons, tumor necrosis factor [TNF], interleukins, or biological response modifiers [granulocyte macrophage colony stimulating factor {GM-CSF}, granulocyte colony stimulating factor {G-CSF}, macrophage-colony stimulating factor {M-CSF}], monoclonal antibodies) within 4 weeks (28 days) prior to randomization
- Receipt of investigational systemic drugs (including off-label use of approved products) within 4 weeks (28 days) prior to randomization
- Metastatic disease
- Malignant pleural effusion at initial diagnosis and/or at study entry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tecemotide (L-BLP25)After receiving cyclophosphamide, participants will receive 8 consecutive weekly subcutaneous vaccinations with 806 microgram (mcg) of tecemotide (L-BLP25) at Weeks 0, 1, 2, 3, 4, 5, 6, and 7 followed by maintenance vaccinations with 806 mcg of tecemotide (L-BLP25) at 6-week intervals, commencing at Week 13, until disease progression is documented. | Biological | Tecemotide (L-BLP25) |
| Single low dose cyclophosphamideA single intravenous infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg) of cyclophosphamide will be given 3 days before first tecemotide (L-BLP25) vaccination. | Drug | Tecemotide (L-BLP25) |
| PlaceboA single infusion (IV) of 0.9% Saline solution instead of cyclophosphamide but in the same calculated dose will be given three days before first placebo vaccination. Subjects will then receive eight consecutive weekly subcutaneous vaccinations with placebo at weeks 0; 1; 2; 3; 4; 5; 6 and 7 followed by maintenance placebo vaccinations at 6-week intervals, commencing at week 13, until disease progression is documented. | Drug | Placebo |
Primary outcome
Overall Survival
Time frame: Up to 66 months
Overall survival time was defined as the time from randomization to death. Participants without events were censored at the last date they were known to be alive or the clinical cut-off date, whatever was earlier.
4 secondary outcomes
Time To Symptom Progression (TTSP) as Measured by the Lung Cancer Symptom Scale (LCSS)
Time frame: Up to 66 months
Time To Progression (TTP)
Time frame: Up to 66 months
One-, Two- and Three-year Survival Rate
Time frame: Years 1, 2, and 3
Number of Participants With Treatment Emergent Adverse Events and Injection Site Reactions
Time frame: From first dose up to 42 days after the last dose of the trial treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundButts C, Socinski MA, Mitchell P, Thatcher N, Havel L, Krzakowski M, Nawrocki S, Ciuleanu TE, Bosquée L, Trigo JM, Spira A, Tremblay L, Nyman J, Ramlau R, Helwig C, Falk MH, Shepherd FA. START: A phase III study of L-BLP25 cancer immunotherapy for unresectable stage III non-small cell lung cancer. American Society of Clinical Oncology - 49th Annual Meeting. 2013; Abstr No. 7500.
- BackgroundShepherd FA, Socinski MA, Mitchell P, Thatcher N, Havel L, Krzakowski M, Nawrocki S, Helwig C, Schroeder A, Butts C. Updated analysis and secondary endpoints with L-BLP25 in unresectable stage III non-small cell lung cancer in the phase III START study. European Society for Medical Oncology 38th Congress - ECCO 17, ESMO 38, ESTRO 32. 2013. Abstr No. 3419.
- BackgroundMitchell P, Butts C, Socinski M, Thatcher N, Wichardt-Johansson G, Ellis P, Gladkov O, Pereira J, Eberhardt W, Horwood K, Szczesna A, Helwig C, Schröder A, Shepherd F. Tecemotide (L-BLP25) in unresectable stage III non-small cell lung cancer in the phase III START study: Further endpoint and exploratory biomarker results. World Conference on Lung Cancer - 15th. 2013; Abstr. No. 2779.
- BackgroundThatcher N, Shepherd FA, Mitchell P, Socinski MA, Paredes A, Lambrechts M, Thomas M, Kollmeier J, Zemanová M, Sadjadian P, Peylan-Ramu N, Helwig C, Schröder A, Butts C. Geographic differences in the combined-modality treatment of stage III unresectable non-small cell lung cancer: Results from a global phase III trial of tecemotide (L-BLP25). World Conference on Lung Cancer - 15th. 2013; Abstr. No. 2712.
- BackgroundSocinski M, Butts C, Mitchell P, Thatcher N, Scagliotti G, Robinet G, Martin C, Zukin M, Ragulin Y, Bonomi P, Yang CH, Regnault A, Helwig C, de Nigris E, Shepherd F. Exploration of patient health status as measured by the generic preference-based questionnaire EQ-5D alongside the START trial of tecemotide in non-small cell lung cancer. World Conference on Lung Cancer - 15th. 2013; Abstr. No. 2744.
- Results publication: PubMed 24331154Butts C, Socinski MA, Mitchell PL, Thatcher N, Havel L, Krzakowski M, Nawrocki S, Ciuleanu TE, Bosquee L, Trigo JM, Spira A, Tremblay L, Nyman J, Ramlau R, Wickart-Johansson G, Ellis P, Gladkov O, Pereira JR, Eberhardt WE, Helwig C, Schroder A, Shepherd FA; START trial team. Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Jan;15(1):59-68. doi: 10.1016/S1470-2045(13)70510-2. Epub 2013 Dec 9.
- Results publication: PubMed 24976972DeGregorio M, Soe L, Wolf M. Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small cell lung cancer (START): a randomized, double-blind, phase III trial. J Thorac Dis. 2014 Jun;6(6):571-3. doi: 10.3978/j.issn.2072-1439.2014.05.15. No abstract available.
- Derived from this study: PubMed 34870327Zhu J, Yuan Y, Wan X, Yin D, Li R, Chen W, Suo C, Song H. Immunotherapy (excluding checkpoint inhibitors) for stage I to III non-small cell lung cancer treated with surgery or radiotherapy with curative intent. Cochrane Database Syst Rev. 2021 Dec 6;12(12):CD011300. doi: 10.1002/14651858.CD011300.pub3.
- Derived from this study: PubMed 25722382Mitchell P, Thatcher N, Socinski MA, Wasilewska-Tesluk E, Horwood K, Szczesna A, Martin C, Ragulin Y, Zukin M, Helwig C, Falk M, Butts C, Shepherd FA. Tecemotide in unresectable stage III non-small-cell lung cancer in the phase III START study: updated overall survival and biomarker analyses. Ann Oncol. 2015 Jun;26(6):1134-1142. doi: 10.1093/annonc/mdv104. Epub 2015 Feb 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany
290 sites in 33 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tecemotide (L-BLP25) and Single low dose cyclophosphamide in people with Non-small Cell Lung Cancer, run by EMD Serono at 290 sites in 33 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 290 sites in United States, Germany, Canada, Italy, Brazil and 28 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: Up to 66 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00409188, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2015.