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

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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Non-small Cell Lung Cancer
Interventions Biological: Tecemotide (L-BLP25)
Drug: Single low dose cyclophosphamide
Drug: Placebo
Enrollment 1513
Recruitment Details First/last participant (informed consent): 25 January 2007/31 October 2011. Data cut-off for primary endpoint analysis: 08 August 2012. Participants randomized at 264 centers in 33 countries worldwide.
Pre-assignment Details A total of 1908 participants were screened for eligibility and 1513 participants were enrolled and randomized.
Arm/Group Title Tecemotide (L-BLP25) + Cyclophosphamide Saline + Placebo
Hide Arm/Group Description A single intravenous infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 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 was documented. A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 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 was documented.
Period Title: Overall Study
Started 1006 507
Completed 623 332
Not Completed 383 175
Reason Not Completed
Ongoing at data cut-off             383             175
Arm/Group Title Tecemotide (L-BLP25) + Cyclophosphamide Saline + Placebo Total
Hide Arm/Group Description A single intravenous infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 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 was documented. A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 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 was documented. Total of all reporting groups
Overall Number of Baseline Participants 1006 507 1513
Hide Baseline Analysis Population Description
ITT population included all the subject who were randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1006 participants 507 participants 1513 participants
60.7  (9.1) 60.9  (9.0) 60.8  (9.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1006 participants 507 participants 1513 participants
Female
315
  31.3%
162
  32.0%
477
  31.5%
Male
691
  68.7%
345
  68.0%
1036
  68.5%
1.Primary Outcome
Title Overall Survival
Hide Description 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.
Time Frame Up to 66 months
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis set (modified intention-to-treat [ITT] population) was based on the ITT population but prospectively excluded all participants (274 participants) that were randomized during the 6 months (22 Sep 2009 to 22 Mar 2010) prior to the effective date of clinical hold.
Arm/Group Title Tecemotide (L-BLP25) + Cyclophosphamide Saline + Placebo
Hide Arm/Group Description:
A single intravenous infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 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 was documented.
A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 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 was documented.
Overall Number of Participants Analyzed 829 410
Median (95% Confidence Interval)
Unit of Measure: months
25.6
(22.5 to 29.2)
22.3
(19.6 to 25.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tecemotide (L-BLP25) + Cyclophosphamide, Saline + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1566
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.893
Confidence Interval (2-Sided) 95%
0.763 to 1.044
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Time To Symptom Progression (TTSP) as Measured by the Lung Cancer Symptom Scale (LCSS)
Hide Description 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 Frame Up to 66 months
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis set (modified ITT population) was based on the ITT population but prospectively excluded all participants (274 participants) that were randomized during the 6 months (22 Sep 2009 to 22 Mar 2010) prior to the effective date of clinical hold. "N" signifies the number of participants who were evaluable for this outcome measure.
Arm/Group Title Tecemotide (L-BLP25) + Cyclophosphamide Saline + Placebo
Hide Arm/Group Description:
A single intravenous infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 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 was documented.
A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 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 was documented.
Overall Number of Participants Analyzed 829 409
Median (95% Confidence Interval)
Unit of Measure: months
14.2
(12.9 to 15.7)
11.4
(9.3 to 13.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tecemotide (L-BLP25) + Cyclophosphamide, Saline + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0226
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.845
Confidence Interval (2-Sided) 95%
0.732 to 0.977
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Time To Progression (TTP)
Hide Description 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.
Time Frame Up to 66 months
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis set (modified ITT population) was based on the ITT population but prospectively excluded all participants (274 participants) that were randomized during the 6 months (22 Sep 2009 to 22 Mar 2010) prior to the effective date of clinical hold.
Arm/Group Title Tecemotide (L-BLP25) + Cyclophosphamide Saline + Placebo
Hide Arm/Group Description:
A single intravenous infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 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 was documented.
A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 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 was documented.
Overall Number of Participants Analyzed 829 410
Median (95% Confidence Interval)
Unit of Measure: months
10.0
(9.1 to 11.5)
8.4
(7.2 to 10.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tecemotide (L-BLP25) + Cyclophosphamide, Saline + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0528
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.868
Confidence Interval (2-Sided) 95%
0.752 to 1.002
Estimation Comments [Not Specified]
4.Secondary Outcome
Title One-, Two- and Three-year Survival Rate
Hide Description 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.
Time Frame Years 1, 2, and 3
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis set (modified ITT population) was based on the ITT population but prospectively excluded all participants (274 participants) that were randomized during the 6 months (22 Sep 2009 to 22 Mar 2010) prior to the effective date of clinical hold.
Arm/Group Title Tecemotide (L-BLP25) + Cyclophosphamide Saline + Placebo
Hide Arm/Group Description:
A single intravenous infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 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 was documented.
A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 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 was documented.
Overall Number of Participants Analyzed 829 410
Measure Type: Number
Unit of Measure: percentage of participants
Year 1 77.0 74.7
Year 2 50.8 45.9
Year 3 40.2 37.0
5.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events and Injection Site Reactions
Hide Description 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.
Time Frame From first dose up to 42 days after the last dose of the trial treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
Arm/Group Title Tecemotide (L-BLP25) + Cyclophosphamide Saline + Placebo
Hide Arm/Group Description:
A single intravenous infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 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 was documented.
A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 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 was documented.
Overall Number of Participants Analyzed 1024 477
Measure Type: Number
Unit of Measure: participants
Treatment Emergent Adverse events 938 432
Injection site reaction 176 56
Time Frame Up to 66 months
Adverse Event Reporting Description Safety analysis set included all participants who received at least 1 dose of trial treatment (cyclophosphamide, tecemotide, saline, or placebo). Participants were reported based on the actual treatment received (as-treated).
 
Arm/Group Title Tecemotide (L-BLP25) + Cyclophosphamide Saline + Placebo
Hide Arm/Group Description A single intravenous infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg) of cyclophosphamide was given 3 days before first tecemotide (L-BLP25) vaccination. After receiving cyclophosphamide, participants received 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 was documented. A single intravenous infusion of 0.9 percent (%) saline solution in the same calculated dose as cyclophosphamide was given 3 days before first placebo vaccination. After receiving saline, participants received 8 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 was documented.
All-Cause Mortality
Tecemotide (L-BLP25) + Cyclophosphamide Saline + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Tecemotide (L-BLP25) + Cyclophosphamide Saline + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   303/1024 (29.59%)   151/477 (31.66%) 
Blood and lymphatic system disorders     
Anaemia * 1  3/1024 (0.29%)  2/477 (0.42%) 
Haemolytic anaemia * 1  0/1024 (0.00%)  1/477 (0.21%) 
Hypocoagulable state * 1  1/1024 (0.10%)  0/477 (0.00%) 
Pancytopenia * 1  3/1024 (0.29%)  0/477 (0.00%) 
Thrombocytopenia * 1  3/1024 (0.29%)  0/477 (0.00%) 
Cardiac disorders     
Acute coronary syndrome * 1  0/1024 (0.00%)  1/477 (0.21%) 
Acute myocardial infarction * 1  1/1024 (0.10%)  4/477 (0.84%) 
Angina pectoris * 1  3/1024 (0.29%)  3/477 (0.63%) 
Arrhythmia * 1  0/1024 (0.00%)  1/477 (0.21%) 
Atrial fibrillation * 1  8/1024 (0.78%)  3/477 (0.63%) 
Atrial flutter * 1  3/1024 (0.29%)  0/477 (0.00%) 
Atrioventricular block second degree * 1  0/1024 (0.00%)  1/477 (0.21%) 
Cardiac disorder * 1  1/1024 (0.10%)  0/477 (0.00%) 
Cardiac failure congestive * 1  0/1024 (0.00%)  1/477 (0.21%) 
Cardiac tamponade * 1  2/1024 (0.20%)  2/477 (0.42%) 
Cardio-respiratory arrest * 1  0/1024 (0.00%)  1/477 (0.21%) 
Cardiomyopathy * 1  1/1024 (0.10%)  1/477 (0.21%) 
Cardiopulmonary failure * 1  0/1024 (0.00%)  1/477 (0.21%) 
Coronary artery disease * 1  1/1024 (0.10%)  0/477 (0.00%) 
Coronary artery occlusion * 1  1/1024 (0.10%)  0/477 (0.00%) 
Coronary artery stenosis * 1  1/1024 (0.10%)  0/477 (0.00%) 
Left ventricular failure * 1  1/1024 (0.10%)  0/477 (0.00%) 
Myocardial infarction * 1  3/1024 (0.29%)  1/477 (0.21%) 
Myocardial ischaemia * 1  2/1024 (0.20%)  0/477 (0.00%) 
Palpitations * 1  1/1024 (0.10%)  0/477 (0.00%) 
Pericardial effusion * 1  3/1024 (0.29%)  1/477 (0.21%) 
Pericarditis * 1  2/1024 (0.20%)  0/477 (0.00%) 
Sick sinus syndrome * 1  0/1024 (0.00%)  2/477 (0.42%) 
Supraventricular tachycardia * 1  1/1024 (0.10%)  0/477 (0.00%) 
Tachycardia * 1  2/1024 (0.20%)  0/477 (0.00%) 
Ventricular fibrillation * 1  0/1024 (0.00%)  1/477 (0.21%) 
Ventricular tachycardia * 1  2/1024 (0.20%)  0/477 (0.00%) 
Ear and labyrinth disorders     
Vertigo * 1  3/1024 (0.29%)  2/477 (0.42%) 
Endocrine disorders     
Adrenal insufficiency * 1  2/1024 (0.20%)  0/477 (0.00%) 
Hypothyroidism * 1  1/1024 (0.10%)  0/477 (0.00%) 
Eye disorders     
Retinal vascular thrombosis * 1  0/1024 (0.00%)  1/477 (0.21%) 
Gastrointestinal disorders     
Abdominal pain * 1  0/1024 (0.00%)  2/477 (0.42%) 
Abdominal pain lower * 1  0/1024 (0.00%)  1/477 (0.21%) 
Abdominal pain upper * 1  1/1024 (0.10%)  0/477 (0.00%) 
Aphagia * 1  1/1024 (0.10%)  0/477 (0.00%) 
Colitis * 1  0/1024 (0.00%)  1/477 (0.21%) 
Constipation * 1  1/1024 (0.10%)  0/477 (0.00%) 
Diarrhoea * 1  0/1024 (0.00%)  1/477 (0.21%) 
Diverticulum intestinal * 1  1/1024 (0.10%)  0/477 (0.00%) 
Duodenal ulcer * 1  1/1024 (0.10%)  0/477 (0.00%) 
Duodenitis * 1  1/1024 (0.10%)  0/477 (0.00%) 
Dyspepsia * 1  0/1024 (0.00%)  1/477 (0.21%) 
Dysphagia * 1  4/1024 (0.39%)  0/477 (0.00%) 
Gastritis * 1  1/1024 (0.10%)  0/477 (0.00%) 
Gastritis erosive * 1  0/1024 (0.00%)  2/477 (0.42%) 
Haemorrhoidal haemorrhage * 1  0/1024 (0.00%)  1/477 (0.21%) 
Hernial eventration * 1  0/1024 (0.00%)  1/477 (0.21%) 
Ileus * 1  1/1024 (0.10%)  0/477 (0.00%) 
Inguinal hernia * 1  0/1024 (0.00%)  2/477 (0.42%) 
Intestinal infarction * 1  1/1024 (0.10%)  0/477 (0.00%) 
Lower gastrointestinal haemorrhage * 1  1/1024 (0.10%)  0/477 (0.00%) 
Oesophageal dilatation * 1  1/1024 (0.10%)  0/477 (0.00%) 
Oesophageal obstruction * 1  2/1024 (0.20%)  0/477 (0.00%) 
Oesophageal stenosis * 1  2/1024 (0.20%)  0/477 (0.00%) 
Pancreatitis * 1  1/1024 (0.10%)  0/477 (0.00%) 
Pancreatitis chronic * 1  1/1024 (0.10%)  0/477 (0.00%) 
Vomiting * 1  1/1024 (0.10%)  3/477 (0.63%) 
General disorders     
Asthenia * 1  2/1024 (0.20%)  3/477 (0.63%) 
Chest discomfort * 1  0/1024 (0.00%)  1/477 (0.21%) 
Chest pain * 1  9/1024 (0.88%)  3/477 (0.63%) 
Death * 1  2/1024 (0.20%)  0/477 (0.00%) 
Disease progression * 1  6/1024 (0.59%)  11/477 (2.31%) 
Fatigue * 1  3/1024 (0.29%)  0/477 (0.00%) 
Gait disturbance * 1  1/1024 (0.10%)  0/477 (0.00%) 
General physical health deterioration * 1  2/1024 (0.20%)  3/477 (0.63%) 
Malaise * 1  1/1024 (0.10%)  0/477 (0.00%) 
Non-cardiac chest pain * 1  4/1024 (0.39%)  1/477 (0.21%) 
Pain * 1  1/1024 (0.10%)  1/477 (0.21%) 
Performance status decreased * 1  0/1024 (0.00%)  1/477 (0.21%) 
Pyrexia * 1  8/1024 (0.78%)  0/477 (0.00%) 
Spinal pain * 1  1/1024 (0.10%)  0/477 (0.00%) 
Hepatobiliary disorders     
Cholecystitis acute * 1  1/1024 (0.10%)  0/477 (0.00%) 
Hepatic failure * 1  1/1024 (0.10%)  0/477 (0.00%) 
Hepatitis alcoholic * 1  1/1024 (0.10%)  0/477 (0.00%) 
Hyperbilirubinaemia * 1  0/1024 (0.00%)  1/477 (0.21%) 
Immune system disorders     
Hypersensitivity * 1  1/1024 (0.10%)  0/477 (0.00%) 
Infections and infestations     
Appendicitis * 1  0/1024 (0.00%)  1/477 (0.21%) 
Bronchitis * 1  4/1024 (0.39%)  1/477 (0.21%) 
Bronchopneumonia * 1  1/1024 (0.10%)  0/477 (0.00%) 
Bronchopulmonary aspergillosis * 1  1/1024 (0.10%)  0/477 (0.00%) 
Cellulitis * 1  1/1024 (0.10%)  0/477 (0.00%) 
Device related infection * 1  1/1024 (0.10%)  0/477 (0.00%) 
Empyema * 1  0/1024 (0.00%)  1/477 (0.21%) 
Gastroenteritis * 1  1/1024 (0.10%)  0/477 (0.00%) 
Helicobacter gastritis * 1  1/1024 (0.10%)  0/477 (0.00%) 
Herpes zoster disseminated * 1  1/1024 (0.10%)  0/477 (0.00%) 
Infectious pleural effusion * 1  1/1024 (0.10%)  0/477 (0.00%) 
Influenza * 1  0/1024 (0.00%)  1/477 (0.21%) 
Lobar pneumonia * 1  1/1024 (0.10%)  0/477 (0.00%) 
Lower respiratory tract infection * 1  9/1024 (0.88%)  4/477 (0.84%) 
Lung abscess * 1  1/1024 (0.10%)  0/477 (0.00%) 
Lung infection * 1  4/1024 (0.39%)  0/477 (0.00%) 
Mastitis * 1  0/1024 (0.00%)  1/477 (0.21%) 
Nasopharyngitis * 1  1/1024 (0.10%)  0/477 (0.00%) 
Pleural infection * 1  1/1024 (0.10%)  0/477 (0.00%) 
Pneumonia * 1  30/1024 (2.93%)  14/477 (2.94%) 
Pneumonia primary atypical * 1  1/1024 (0.10%)  0/477 (0.00%) 
Respiratory tract infection * 1  7/1024 (0.68%)  2/477 (0.42%) 
Salmonella sepsis * 1  0/1024 (0.00%)  1/477 (0.21%) 
Septic shock * 1  1/1024 (0.10%)  1/477 (0.21%) 
Upper respiratory tract infection * 1  2/1024 (0.20%)  0/477 (0.00%) 
Viral upper respiratory tract infection * 1  0/1024 (0.00%)  1/477 (0.21%) 
Injury, poisoning and procedural complications     
Ankle fracture * 1  1/1024 (0.10%)  0/477 (0.00%) 
Cervical vertebral fracture * 1  1/1024 (0.10%)  1/477 (0.21%) 
Clavicle fracture * 1  0/1024 (0.00%)  1/477 (0.21%) 
Concussion * 1  1/1024 (0.10%)  0/477 (0.00%) 
Craniocerebral injury * 1  0/1024 (0.00%)  1/477 (0.21%) 
Fall * 1  0/1024 (0.00%)  1/477 (0.21%) 
Femoral neck fracture * 1  1/1024 (0.10%)  1/477 (0.21%) 
Femur fracture * 1  1/1024 (0.10%)  1/477 (0.21%) 
Foot fracture * 1  2/1024 (0.20%)  0/477 (0.00%) 
Hip fracture * 1  0/1024 (0.00%)  1/477 (0.21%) 
Humerus fracture * 1  1/1024 (0.10%)  0/477 (0.00%) 
Laceration * 1  1/1024 (0.10%)  0/477 (0.00%) 
Lower limb fracture * 1  1/1024 (0.10%)  0/477 (0.00%) 
Lumbar vertebral fracture * 1  0/1024 (0.00%)  1/477 (0.21%) 
Meniscus lesion * 1  0/1024 (0.00%)  1/477 (0.21%) 
Overdose * 1  1/1024 (0.10%)  0/477 (0.00%) 
Procedural complication * 1  1/1024 (0.10%)  0/477 (0.00%) 
Procedural pain * 1  1/1024 (0.10%)  0/477 (0.00%) 
Radiation associated pain * 1  1/1024 (0.10%)  0/477 (0.00%) 
Radiation myelopathy * 1  0/1024 (0.00%)  1/477 (0.21%) 
Radiation pneumonitis * 1  7/1024 (0.68%)  5/477 (1.05%) 
Rib fracture * 1  1/1024 (0.10%)  0/477 (0.00%) 
Road traffic accident * 1  1/1024 (0.10%)  0/477 (0.00%) 
Spinal compression fracture * 1  1/1024 (0.10%)  0/477 (0.00%) 
Thoracic vertebral fracture * 1  1/1024 (0.10%)  0/477 (0.00%) 
Traumatic lung injury * 1  1/1024 (0.10%)  0/477 (0.00%) 
Vascular pseudoaneurysm * 1  1/1024 (0.10%)  0/477 (0.00%) 
Wound evisceration * 1  1/1024 (0.10%)  0/477 (0.00%) 
Investigations     
Weight decreased * 1  1/1024 (0.10%)  0/477 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  2/1024 (0.20%)  0/477 (0.00%) 
Dehydration * 1  4/1024 (0.39%)  1/477 (0.21%) 
Diabetes mellitus inadequate control * 1  1/1024 (0.10%)  0/477 (0.00%) 
Hypercalcaemia * 1  0/1024 (0.00%)  2/477 (0.42%) 
Hyperkalaemia * 1  0/1024 (0.00%)  1/477 (0.21%) 
Hyponatraemia * 1  0/1024 (0.00%)  1/477 (0.21%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  0/1024 (0.00%)  2/477 (0.42%) 
Arthritis * 1  1/1024 (0.10%)  0/477 (0.00%) 
Back pain * 1  1/1024 (0.10%)  2/477 (0.42%) 
Bone pain * 1  1/1024 (0.10%)  0/477 (0.00%) 
Muscle atrophy * 1  1/1024 (0.10%)  0/477 (0.00%) 
Muscular weakness * 1  0/1024 (0.00%)  1/477 (0.21%) 
Musculoskeletal pain * 1  1/1024 (0.10%)  1/477 (0.21%) 
Pain in extremity * 1  2/1024 (0.20%)  1/477 (0.21%) 
Pathological fracture * 1  1/1024 (0.10%)  0/477 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma * 1  2/1024 (0.20%)  2/477 (0.42%) 
Bile duct cancer * 1  1/1024 (0.10%)  0/477 (0.00%) 
Bladder cancer * 1  1/1024 (0.10%)  2/477 (0.42%) 
Breast cancer * 1  1/1024 (0.10%)  0/477 (0.00%) 
Colon cancer * 1  1/1024 (0.10%)  0/477 (0.00%) 
Gastric cancer * 1  1/1024 (0.10%)  0/477 (0.00%) 
Lung cancer metastatic * 1  1/1024 (0.10%)  0/477 (0.00%) 
Malignant pleural effusion * 1  0/1024 (0.00%)  1/477 (0.21%) 
Meningioma * 1  1/1024 (0.10%)  0/477 (0.00%) 
Metastases to bone * 1  1/1024 (0.10%)  1/477 (0.21%) 
Metastases to central nervous system * 1  32/1024 (3.13%)  9/477 (1.89%) 
Metastases to kidney * 1  2/1024 (0.20%)  1/477 (0.21%) 
Metastases to large intestine * 1  1/1024 (0.10%)  0/477 (0.00%) 
Metastases to lung * 1  1/1024 (0.10%)  0/477 (0.00%) 
Metastases to lymph nodes * 1  1/1024 (0.10%)  0/477 (0.00%) 
Metastases to pancreas * 1  1/1024 (0.10%)  0/477 (0.00%) 
Metastases to salivary gland * 1  1/1024 (0.10%)  0/477 (0.00%) 
Metastases to small intestine * 1  1/1024 (0.10%)  0/477 (0.00%) 
Oncologic complication * 1  1/1024 (0.10%)  0/477 (0.00%) 
Paraneoplastic syndrome * 1  0/1024 (0.00%)  1/477 (0.21%) 
Prostate cancer * 1  1/1024 (0.10%)  0/477 (0.00%) 
Prostatic adenoma * 1  1/1024 (0.10%)  1/477 (0.21%) 
Renal cell carcinoma * 1  0/1024 (0.00%)  1/477 (0.21%) 
Thyroid neoplasm * 1  0/1024 (0.00%)  1/477 (0.21%) 
Tonsil cancer * 1  1/1024 (0.10%)  0/477 (0.00%) 
Tumour invasion * 1  1/1024 (0.10%)  1/477 (0.21%) 
Tumour pain * 1  1/1024 (0.10%)  0/477 (0.00%) 
Nervous system disorders     
Altered state of consciousness * 1  1/1024 (0.10%)  0/477 (0.00%) 
Aphasia * 1  1/1024 (0.10%)  1/477 (0.21%) 
Balance disorder * 1  1/1024 (0.10%)  0/477 (0.00%) 
Brain oedema * 1  1/1024 (0.10%)  0/477 (0.00%) 
Carotid artery dissection * 1  1/1024 (0.10%)  0/477 (0.00%) 
Carotid artery occlusion * 1  1/1024 (0.10%)  0/477 (0.00%) 
Cataplexy * 1  0/1024 (0.00%)  1/477 (0.21%) 
Cerebral ischaemia * 1  0/1024 (0.00%)  2/477 (0.42%) 
Cerebrovascular accident * 1  0/1024 (0.00%)  2/477 (0.42%) 
Convulsion * 1  4/1024 (0.39%)  2/477 (0.42%) 
Dizziness * 1  4/1024 (0.39%)  0/477 (0.00%) 
Epilepsy * 1  2/1024 (0.20%)  2/477 (0.42%) 
Grand mal convulsion * 1  1/1024 (0.10%)  0/477 (0.00%) 
Guillain-Barre syndrome * 1  1/1024 (0.10%)  0/477 (0.00%) 
Haemorrhage intracranial * 1  1/1024 (0.10%)  0/477 (0.00%) 
Headache * 1  3/1024 (0.29%)  0/477 (0.00%) 
Hemiparesis * 1  4/1024 (0.39%)  0/477 (0.00%) 
Ischaemic cerebral infarction * 1  1/1024 (0.10%)  0/477 (0.00%) 
Ischaemic stroke * 1  1/1024 (0.10%)  1/477 (0.21%) 
Monoparesis * 1  1/1024 (0.10%)  0/477 (0.00%) 
Nerve root compression * 1  1/1024 (0.10%)  0/477 (0.00%) 
Paraplegia * 1  1/1024 (0.10%)  0/477 (0.00%) 
Partial seizures * 1  1/1024 (0.10%)  1/477 (0.21%) 
Peripheral motor neuropathy * 1  0/1024 (0.00%)  1/477 (0.21%) 
Somnolence * 1  0/1024 (0.00%)  1/477 (0.21%) 
Spinal cord compression * 1  1/1024 (0.10%)  1/477 (0.21%) 
Status epilepticus * 1  0/1024 (0.00%)  1/477 (0.21%) 
Syncope * 1  4/1024 (0.39%)  1/477 (0.21%) 
Transient ischaemic attack * 1  2/1024 (0.20%)  0/477 (0.00%) 
Tremor * 1  0/1024 (0.00%)  1/477 (0.21%) 
Psychiatric disorders     
Anxiety * 1  0/1024 (0.00%)  1/477 (0.21%) 
Completed suicide * 1  1/1024 (0.10%)  0/477 (0.00%) 
Confusional state * 1  3/1024 (0.29%)  1/477 (0.21%) 
Depression * 1  1/1024 (0.10%)  1/477 (0.21%) 
Mental status changes * 1  0/1024 (0.00%)  1/477 (0.21%) 
Suicide attempt * 1  2/1024 (0.20%)  0/477 (0.00%) 
Renal and urinary disorders     
Haematuria * 1  1/1024 (0.10%)  0/477 (0.00%) 
Urinary retention * 1  1/1024 (0.10%)  0/477 (0.00%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia * 1  1/1024 (0.10%)  0/477 (0.00%) 
Ovarian cyst * 1  0/1024 (0.00%)  1/477 (0.21%) 
Spermatocele * 1  1/1024 (0.10%)  0/477 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure * 1  2/1024 (0.20%)  0/477 (0.00%) 
Atelectasis * 1  2/1024 (0.20%)  0/477 (0.00%) 
Bronchial haemorrhage * 1  0/1024 (0.00%)  1/477 (0.21%) 
Bronchial obstruction * 1  0/1024 (0.00%)  1/477 (0.21%) 
Bronchitis chronic * 1  1/1024 (0.10%)  0/477 (0.00%) 
Bronchostenosis * 1  1/1024 (0.10%)  0/477 (0.00%) 
Chronic obstructive pulmonary disease * 1  3/1024 (0.29%)  7/477 (1.47%) 
Cough * 1  3/1024 (0.29%)  1/477 (0.21%) 
Dysphonia * 1  1/1024 (0.10%)  0/477 (0.00%) 
Dyspnoea * 1  29/1024 (2.83%)  13/477 (2.73%) 
Epistaxis * 1  2/1024 (0.20%)  0/477 (0.00%) 
Haemoptysis * 1  11/1024 (1.07%)  5/477 (1.05%) 
Hypoxia * 1  2/1024 (0.20%)  0/477 (0.00%) 
Laryngeal cyst * 1  1/1024 (0.10%)  0/477 (0.00%) 
Lung infiltration * 1  1/1024 (0.10%)  0/477 (0.00%) 
Oesophagobronchial fistula * 1  1/1024 (0.10%)  0/477 (0.00%) 
Pleural effusion * 1  13/1024 (1.27%)  12/477 (2.52%) 
Pleurisy * 1  1/1024 (0.10%)  2/477 (0.42%) 
Pneumonitis * 1  2/1024 (0.20%)  1/477 (0.21%) 
Pneumothorax * 1  6/1024 (0.59%)  1/477 (0.21%) 
Pulmonary embolism * 1  10/1024 (0.98%)  2/477 (0.42%) 
Pulmonary haemorrhage * 1  8/1024 (0.78%)  4/477 (0.84%) 
Pulmonary hypertension * 1  1/1024 (0.10%)  0/477 (0.00%) 
Pulmonary oedema * 1  0/1024 (0.00%)  1/477 (0.21%) 
Respiratory failure * 1  0/1024 (0.00%)  4/477 (0.84%) 
Skin and subcutaneous tissue disorders     
Rash * 1  1/1024 (0.10%)  1/477 (0.21%) 
Surgical and medical procedures     
Pericardial drainage * 1  1/1024 (0.10%)  0/477 (0.00%) 
Vascular disorders     
Aortic aneurysm * 1  5/1024 (0.49%)  1/477 (0.21%) 
Aortic stenosis * 1  0/1024 (0.00%)  1/477 (0.21%) 
Arterial occlusive disease * 1  1/1024 (0.10%)  0/477 (0.00%) 
Deep vein thrombosis * 1  0/1024 (0.00%)  1/477 (0.21%) 
Embolism * 1  1/1024 (0.10%)  0/477 (0.00%) 
Femoral arterial stenosis * 1  1/1024 (0.10%)  0/477 (0.00%) 
Hypotension * 1  2/1024 (0.20%)  0/477 (0.00%) 
Orthostatic hypotension * 1  0/1024 (0.00%)  1/477 (0.21%) 
Peripheral arterial occlusive disease * 1  1/1024 (0.10%)  0/477 (0.00%) 
Peripheral artery aneurysm * 1  1/1024 (0.10%)  0/477 (0.00%) 
Peripheral vascular disorder * 1  0/1024 (0.00%)  1/477 (0.21%) 
Temporal arteritis * 1  0/1024 (0.00%)  1/477 (0.21%) 
Thrombosis * 1  0/1024 (0.00%)  1/477 (0.21%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 13.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tecemotide (L-BLP25) + Cyclophosphamide Saline + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   918/1024 (89.65%)   417/477 (87.42%) 
Gastrointestinal disorders     
Constipation * 1  75/1024 (7.32%)  26/477 (5.45%) 
Diarrhoea * 1  85/1024 (8.30%)  46/477 (9.64%) 
Nausea * 1  140/1024 (13.67%)  39/477 (8.18%) 
Vomiting * 1  65/1024 (6.35%)  26/477 (5.45%) 
General disorders     
Asthenia * 1  71/1024 (6.93%)  29/477 (6.08%) 
Chest pain * 1  130/1024 (12.70%)  43/477 (9.01%) 
Fatigue * 1  195/1024 (19.04%)  102/477 (21.38%) 
Influenza like illness * 1  45/1024 (4.39%)  27/477 (5.66%) 
Non-cardiac chest pain * 1  57/1024 (5.57%)  24/477 (5.03%) 
Pyrexia * 1  80/1024 (7.81%)  41/477 (8.60%) 
Infections and infestations     
Bronchitis * 1  83/1024 (8.11%)  38/477 (7.97%) 
Nasopharyngitis * 1  128/1024 (12.50%)  44/477 (9.22%) 
Upper respiratory tract infection * 1  96/1024 (9.38%)  37/477 (7.76%) 
Injury, poisoning and procedural complications     
Radiation pneumonitis * 1  77/1024 (7.52%)  30/477 (6.29%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  109/1024 (10.64%)  44/477 (9.22%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  108/1024 (10.55%)  33/477 (6.92%) 
Back pain * 1  146/1024 (14.26%)  52/477 (10.90%) 
Musculoskeletal chest pain * 1  54/1024 (5.27%)  22/477 (4.61%) 
Musculoskeletal pain * 1  92/1024 (8.98%)  33/477 (6.92%) 
Myalgia * 1  73/1024 (7.13%)  18/477 (3.77%) 
Pain in extremity * 1  69/1024 (6.74%)  29/477 (6.08%) 
Nervous system disorders     
Dizziness * 1  87/1024 (8.50%)  37/477 (7.76%) 
Headache * 1  123/1024 (12.01%)  54/477 (11.32%) 
Psychiatric disorders     
Insomnia * 1  64/1024 (6.25%)  25/477 (5.24%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  336/1024 (32.81%)  133/477 (27.88%) 
Dyspnoea * 1  225/1024 (21.97%)  103/477 (21.59%) 
Haemoptysis * 1  60/1024 (5.86%)  32/477 (6.71%) 
Skin and subcutaneous tissue disorders     
Rash * 1  53/1024 (5.18%)  27/477 (5.66%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 13.0
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
After conclusion of the study, an integrated clinical and statistical study report shall be written by the Sponsor in consultation with the Coordinating Investigator based on the protocol. The first publication will be a full publication of all data from all sites. The Sponsor is entitled to delay publication in order to obtain patent protection. The ICMJE criteria for authorship will be followed. A separate publication plan will be set up to describe further publications.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Merck KGaA Communication Center
Organization: Merck Serono, a division of Merck KGaA
Phone: +49-6151-72-5200
EMail: service@merckgroup.com
Publications of Results:
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.
DeGregorio 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.
Other 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.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00409188    
Other Study ID Numbers: EMR 63325-001
First Submitted: December 7, 2006
First Posted: December 8, 2006
Results First Submitted: July 23, 2015
Results First Posted: November 20, 2015
Last Update Posted: November 20, 2015