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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00409188
Recruitment Status : Completed
First Posted : December 8, 2006
Results First Posted : November 20, 2015
Last Update Posted : November 20, 2015
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono

Tracking Information
First Submitted Date  ICMJE December 7, 2006
First Posted Date  ICMJE December 8, 2006
Results First Submitted Date  ICMJE July 23, 2015
Results First Posted Date  ICMJE November 20, 2015
Last Update Posted Date November 20, 2015
Study Start Date  ICMJE January 2007
Actual Primary Completion Date April 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2015)		 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 7, 2006)		 To compare survival duration of all randomized subjects by treatment arm
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2015)
  • Time To Symptom Progression (TTSP) as Measured by the Lung Cancer Symptom Scale (LCSS) [ Time Frame: 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) [ Time Frame: 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 Rate [ Time Frame: Years 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 Reactions [ Time Frame: From 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2006)
  • to compare all randomized subjects by treatment arm for: Time To Symptom Progression (TTSP) as measured by the Lung Cancer Symptom Scale (LCSS)
  • Time To Progression (TTP) as determined by the investigator
  • one-, two- and three-year survival
  • Safety
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cancer Vaccine Study for Unresectable Stage III Non-small Cell Lung Cancer (START)
Official Title  ICMJE 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.
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)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE
  • Biological: 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.
  • Drug: Single low dose cyclophosphamide
    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.
  • Drug: Placebo
    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 Arms  ICMJE
  • Experimental: Tecemotide (L-BLP25)
    Interventions:
    • Biological: Tecemotide (L-BLP25)
    • Drug: Single low dose cyclophosphamide
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 19, 2013)		 1513
Original Enrollment  ICMJE
 (submitted: December 7, 2006)		 1322
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date April 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   China,   Czech Republic,   Denmark,   France,   Germany,   Greece,   Hong Kong,   Hungary,   India,   Ireland,   Israel,   Italy,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Portugal,   Romania,   Russian Federation,   Singapore,   Slovakia,   Spain,   Sweden,   Switzerland,   Taiwan,   United Kingdom,   United States
Removed Location Countries Ukraine
 
Administrative Information
NCT Number  ICMJE NCT00409188
Other Study ID Numbers  ICMJE EMR 63325-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party EMD Serono
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE EMD Serono
Original Study Sponsor  ICMJE Merck KGaA, Darmstadt, Germany
Collaborators  ICMJE Merck KGaA, Darmstadt, Germany
Investigators  ICMJE
Study Director: Medical Responsible EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany
PRS Account EMD Serono
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP