Safety Study of Tecemotide (L-BLP25) in Non-Small Cell Lung Cancer (NSCLC) Subjects With Unresectable Stage III Disease

Study Overview
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Brief Summary
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The primary objective is to document the safety of tecemotide (L-BLP25) phase III formulation in non-small cell lung cancer (NSCLC) subjects with unresectable Stage III disease. This population includes Stage IIIA NSCLC subjects, a population not studied in former clinical studies with this vaccine. The secondary objective is to document the survival of subjects treated.

Official Title
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A Multi-center, Non-randomized, Open Label Safety Study of BLP25 Liposome Vaccine (L-BLP25) in Non-Small Cell Lung Cancer (NSCLC) Patients With Unresectable Stage III Disease

Conditions
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Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

Intervention / Treatment
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* Biological: Tecemotide (L-BLP25)
* Drug: Single low dose cyclophosphamide
* Other: Best standard of care (BSC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented unresectable stage III NSCLC. Mediastinal (N2) involvement must be confirmed by biopsy Stable disease or clinical response after primary therapy of chemo-radiation treatment for unresectable stage III disease Primary therapy should be a minimum of 2 cycles of Platinum-based first-line chemotherapy, given concurrent with thoracic radiation. The combined modality should consist of either: induction (2 cycles) chemotherapy followed by concurrent chemo-radiation therapy; or concurrent chemo-radiation therapy followed by 2 cycles of consolidation chemotherapy; or concurrent chemoradiation therapy alone A minimum radiation dose of greater than or equal to (>=) 6,000 centigray (cGy) should be administered. Subjects must have completed the primary therapy at least 4 weeks and no later than 6 months prior to study entry Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to (<=) 1 Ability to understand and willingness to sign a written informed consent Other protocol defined inclusion criteria could apply Exclusion Criteria: Undergone lung cancer specific therapy (including surgery) prior to primary chemo-radiation therapy Received immunotherapy/systemic immunosuppressive drugs/investigational systemic drugs within 4 weeks prior to study entry Subjects with brain metastases, pleural effusion, unless cytologically confirmed to be non-malignant 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 or immunodeficiency Clinically significant hepatic, renal dysfunction or cardiac diseases Clinically significant active infection Pregnant or lactating, women of childbearing potential, unless using effective contraception as determined by the investigator Other protocol defined inclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tecemotide(L-BLP25)+Cyclophosphomide+best standard of care<br> | Biological: Tecemotide (L-BLP25)<br>* After receiving single low-dose cyclophosphamide, subjects will receive 8 consecutive weekly subcutaneous vaccinations with 1000 microgram (mcg) of tecemotide (L-BLP25) at weeks 0, 1, 2, 3, 4, 5, 6 and 7 followed by maintenance vaccinations (1000 mcg of tecemotide [L-BLP25]) at 6-week intervals, commencing at Week 13, until disease progression is documented.<br>Drug: Single low dose cyclophosphamide<br>* A single intravenous infusion of 300 milligram per square meter (mg/m^2) (to a maximum 600 mg) of cyclophosphamide will be administered 3 days prior to tecemotide (L-BLP25), the first vaccine treatment.<br>Other: Best standard of care (BSC)<br>* The BSC will be provided at the investigator's discretion, and may include but not be limited to psychosocial support, nutritional support and other supportive therapies.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs With CALGB-ECTC Grade 3 or 4, TEAEs Leading to Discontinuation, TEAEs Leading to Death, and Injection Site Reactions (ISRs) | TEAEs occurred between the first dose of study drug and up to 42 days after the last dose that were absent before treatment or that worsened relative to pretreatment state. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs with Cancer and Leukemia Group B Extended Clinical Toxicity Criteria (CALGB-ECTC) Grade 3 or 4 were also reported. | Up to data cut-off date (17 September 2007) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival Time | Survival time was to be measured from study entry (date of cyclophosphamide administration) to date of death. For subjects alive or lost to follow-up at time of analysis, the time between date of cyclophosphamide administration and date on which the subject was last known alive was to be calculated and used as a censored observation in the analysis. | Up to data cut-off date (17 September 2007) | 
| Progression Free Survival (PFS) Time | PFS was defined as duration from first administration of trial treatment until progressive disease [PD] (radiological or clinical, if radiological progression is not available) or death due to any cause. Participants without event were censored on the date of last tumor assessment. Clinical assessments were performed 4 weekly in primary treatment and 6 weekly in maintenance treatment. | Up to data cut-off date (17 September 2007) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carcinoma, Non-Small-Cell Lung, L-BLP25, Tecemotide