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Cancer Vaccine Study for Unresectable Stage III Non-small Cell Lung Cancer (START)

Phase 3
Completed
Conditions
Non-small Cell Lung Cancer
Interventions
Drug: Placebo
Biological: Tecemotide (L-BLP25)
Registration Number
NCT00409188
Lead Sponsor
EMD Serono
Brief 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.

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)

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1513
Inclusion Criteria
  • 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)
Exclusion Criteria

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
  • 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo-
Tecemotide (L-BLP25)Tecemotide (L-BLP25)-
Tecemotide (L-BLP25)Single low dose cyclophosphamide-
Primary Outcome Measures
NameTimeMethod
Overall SurvivalUp 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.

Secondary Outcome Measures
NameTimeMethod
Time To Symptom Progression (TTSP) as Measured by the Lung Cancer Symptom Scale (LCSS)Up to 66 months

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.

Time To Progression (TTP)Up to 66 months

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.

One-, Two- and Three-year Survival RateYears 1, 2, and 3

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.

Number of Participants With Treatment Emergent Adverse Events and Injection Site ReactionsFrom first dose up to 42 days after the last dose of the trial treatment

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.

Trial Locations

Locations (93)

Deaconess Billings Clinic

🇺🇸

Billings, Montana, United States

University of Maryland, Marlene and Steward Greenbaum Cancer Center

🇺🇸

Baltimore, Maryland, United States

Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute

🇺🇸

Los Angeles, California, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

Sinai Hospital of Baltimore

🇺🇸

Baltimore, Maryland, United States

Univ. of Pennsylvania Abramson Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

Southern Illinois Hematology/Oncology

🇺🇸

Centralia, Illinois, United States

Norris Cancer Hospital

🇺🇸

Los Angeles, California, United States

Desert Hematology Oncology Medical Group, Inc

🇺🇸

Rancho Mirage, California, United States

Big Sky Oncology, Sletten Cancer Institute

🇺🇸

Great Falls, Montana, United States

Carolinas Hematology-Oncology

🇺🇸

Charlotte, North Carolina, United States

St. Vincents Comprehensive Cancer Center

🇺🇸

New York, New York, United States

Fairfax-Northern Virginia Hematology Oncology, PC

🇺🇸

Fairfax, Virginia, United States

Fox Chase Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

Centro Oncologico de Roario

🇦🇷

Rosario, Santa Fe, Argentina

Research Site

🇬🇧

Wirral, United Kingdom

Clinica Universitaria Reina Fabiola

🇦🇷

Cordoba, Argentina

Center for Oncology Research

🇺🇸

Dallas, Texas, United States

Frazer Valley Cancer Center

🇨🇦

Surrey, British Columbia, Canada

Hospital Nossa Senhora da Conceicao, Centro de Pesquisas Medicas e Ensaios Clinicos

🇧🇷

Porto Alegre, Rio Grande Do Sol, Brazil

The Center for Cancer and Blood Disorders

🇺🇸

Fort Worth, Texas, United States

Niagara Health System

🇨🇦

Saint Catharines, Ontario, Canada

Capital District Health Authority

🇨🇦

Halifax, Nova Scotia, Canada

Wheeling Hospital

🇺🇸

Wheeling, West Virginia, United States

Paliar

🇦🇷

Capital, Buenos Aires, Buenos Aires, Argentina

Cancer Care Manitoba

🇨🇦

Winnipeg, Manitoba, Canada

Instituto Especializado Alexander Fleming

🇦🇷

Ciudad Autonoma de Buenos Aires, Argentina

Fundacao Hospital Amaral Carvalho

🇧🇷

Jau, Sao Paulo, Brazil

Mount Sinai Hospital

🇨🇦

Toronto, Ontario, Canada

Cross Cancer Institue

🇨🇦

Edmonton, Alberta, Canada

Consultorio del

🇲🇽

Morelia, Michoacan, Mexico

Centro Oncologico de Chihuahua

🇲🇽

Chihuahua, Mexico

Vancouver Island Cancer Center

🇨🇦

Victoria, British Columbia, Canada

Juravinski Cancer Center

🇨🇦

Hamilton, Ontario, Canada

Cape Breton Districk Health Authority Cancer Care

🇨🇦

Sydney, Nova Scotia, Canada

Nugieo de Oncologia da Bahia

🇧🇷

Salvador, Bahia, Brazil

Hospital Sao Lucas-Pucrs

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

Associacao Hospital de Caridade Ijui

🇧🇷

Ijuí, Rio Grande Do Sul, Brazil

Hospital LifeCenter

🇧🇷

Belo Horizonte, Minas Gerais, Brazil

Glendale Adventist Medical Center

🇺🇸

Glendale, California, United States

Hopital Laval

🇨🇦

Sainte-Foy, Quebec, Canada

Hospital das Clinicas da Faculdade de Medinina de Univeridade

🇧🇷

São Paulo, De ao Paulo, Brazil

Instituto de Oncologia de Sorocaba

🇧🇷

Sorocaba, Sao Paulo, Brazil

Instituto Nacional do Cancer - INCA

🇧🇷

Rio de Janeriro, Brazil

Instituto do Cancer Arnaldo Vieira de Caralho-Onco-pneumonia

🇧🇷

Sao Paulo, Brazil

Santa Casa de Misericordia De Sao Paulo

🇧🇷

Sao Paulo, Brazil

Pasco Hernando Oncology Associates P.A

🇺🇸

Brooksville, Florida, United States

Joliet Oncology-Hematology Associates, Ltd.

🇺🇸

Joliet, Illinois, United States

Hematology and Oncology Specialists, LLC

🇺🇸

Metarie, Louisiana, United States

Southeast Nebraska Cancer Center

🇺🇸

Lincoln, Nebraska, United States

Gabrail Cancer Center

🇺🇸

Canton, Ohio, United States

Hanover Medical Specialts PA

🇺🇸

Wilmington, North Carolina, United States

Southwestern Regional Medical Center

🇺🇸

Tulsa, Oklahoma, United States

Signal Point Clinical Research Center, LLC

🇺🇸

Middletown, Ohio, United States

University Hospitals of Cleveland

🇺🇸

Cleveland, Ohio, United States

John Peter Smith Center for Cancer Care

🇺🇸

Fort Worth, Texas, United States

Corporacion Medica General San Martin

🇦🇷

San Martin, Buenos Aires, Argentina

Hospital Italiano Regional del Sur

🇦🇷

Bahia Blanca, Buenos Aires, Argentina

Centro de Educacion Medica e Investigaciones Clinicas "Norberto Quirno" (CEMIC)

🇦🇷

Ciudad Autonoma de Buenos Aires, Argentina

Sociedad Intaliana de Beneficencia en Buenos Aires, Hospital Italiano

🇦🇷

Ciudad Autonoma de Buenos Aires, Argentina

Hospital de Clinicas de Porto Alegre, Dept. de Endocrinologia

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

Centro de Oncologia de Campinas - OCC

🇧🇷

Campinas, Sao Paulo, Brazil

Tom Baker Cancer Center

🇨🇦

Calgary, Alberta, Canada

Hopital Notre Dame

🇨🇦

Montreal, Quebec, Canada

British Columbia Cancer Agency

🇨🇦

Vancouver, British Columbia, Canada

Windsor Regional Cancer Center

🇨🇦

Windsor, Ontario, Canada

Jewish General Hospital

🇨🇦

Montreal, Quebec, Canada

Instituto Nacional de Cancerologia (INCAN)

🇲🇽

Mexico City, Mexico

Genova

🇷🇺

Chelaybinsk, Russian Federation

Reseaerch Site

🇷🇺

Kazan, Tatarstan, Russian Federation

Nebraska Cancer Care, LLC

🇺🇸

Hastings, Nebraska, United States

Reseach Site

🇩🇪

Heidelberg, Germany

Saint Edward Mercy Medical Center

🇺🇸

Fort Smith, Arkansas, United States

Clinical Trials and Research Associates, Inc.

🇺🇸

Montebello, California, United States

Pasco Hernando Oncology Associates, PA

🇺🇸

New Port Richey, Florida, United States

Pacific Cancer Medical Center

🇺🇸

Anaheim, California, United States

Florida Hospital Memorial System

🇺🇸

Ormond Beach, Florida, United States

Stockton Hematology Oncology Medical Group, Inc.

🇺🇸

Stockton, California, United States

Leonard J. Chabert Medical Center

🇺🇸

Houma, Louisiana, United States

Lahey Clinic

🇺🇸

Burlington, Massachusetts, United States

Kentucky Cancer Center

🇺🇸

Hazard, Kentucky, United States

Saint Louis University Cance Center

🇺🇸

Saint Louis, Missouri, United States

Hematology Oncology Associates of Rockland

🇺🇸

Nyack, New York, United States

The Jones Clinic, PC

🇺🇸

Germantown, Tennessee, United States

University of Miami, Sylvester Comprehensive Cancer Center

🇺🇸

Miami, Florida, United States

University of Colorado Cancer Center

🇺🇸

Denver, Colorado, United States

University of Minnesota Physicians, Masonic Cancer Center

🇺🇸

Minneapolis, Minnesota, United States

Univ. of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center

🇺🇸

Chapel Hill, North Carolina, United States

Providence Portland Medical Center

🇺🇸

Portland, Oregon, United States

Cancer Therapy & Research Center, Institute for Drug Development

🇺🇸

San Antonio, Texas, United States

Oncology Care Associates

🇺🇸

Saint Joseph, Michigan, United States

Thunder Bay Regional Health Science Center Northwestern Ontario Regional Center

🇨🇦

Thunder Bay, Ontario, Canada

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