Phase 2b Randomized Controlled Study of Tecemotide (L-BLP25) for Immunotherapy of NSCLC (Non-Small Cell Lung Cancer)

Study Overview
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Brief Summary
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This is a prospective open label, controlled, randomized study to test the safety and efficacy of active specific immunotherapy with tecemotide (L-BLP25) for the treatment of subjects with Stage IIIB or Stage IV non-small cell lung cancer (NSCLC). To be eligible, subjects entering the trial will have to demonstrate either stable disease or a clinical response after first-line treatment (chemotherapy alone, or chemotherapy and radiotherapy) and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. Following a 3 week washout period, subjects will be stratified by disease status (either Stage IIIB locoregional disease or Stage IIIB with malignant pleural effusion and Stage IV), and randomized to either best supportive care (BSC) plus tecemotide (L-BLP25) treatment or BSC alone.

Official Title
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A Multicenter Phase IIb Randomised, Controlled Study of BLP25 Liposome Vaccine for Active Specific Immunotherapy of Non-Small Cell Lung Cancer

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

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage IIIB or Stage IV NSCLC Stable disease or a clinical response following first-line treatment, consisting of either chemotherapy alone or chemotherapy and radiotherapy. Subjects must have completed the first-line treatment at least 3 weeks prior to study entry Eastern Cooperative Oncology Group (ECOG) performance status of greater than or equal to (>=) 2 Ability to understand and willingness to sign a written informed consent Other protocol-defined inclusion criteria could apply Exclusion Criteria: Received immunotherapy within 4 weeks prior to study entry Received immunosuppressive drugs within 3 weeks prior to study entry Subjects with known brain metastases 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 or cardiac dysfunction Subjects with clinically significant active infection Pregnant or breast feeding women, women of childbearing potential, unless using effective contraception as determined by the investigator Other protocol-defined exclusion 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tecemotide (L-BLP25) plus Best Supportive Care (BSC)<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 discontinuation from the study due to ECOG status of 4, participation in alternate trial, serious adverse event, or reasons that preclude assessment of clinical status in the opinion of the investigator, and in case of unavailability of study vaccine.<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 given 3 days before the first vaccine treatment.<br>Other: Best Supportive Care (BSC)<br>* The BSC will be provided at the investigator's discretion, and may include palliative radiation, psychosocial support, analgesics and nutritional support. Second-line chemotherapy is permitted when indicated for treatment of progressive disease.<br>|
| Active Comparator: Best Supportive Care (BSC) Alone<br> | Other: Best Supportive Care (BSC)<br>* The BSC will be provided at the investigator's discretion, and may include palliative radiation, psychosocial support, analgesics and nutritional support. Second-line chemotherapy is permitted when indicated for treatment of progressive disease.<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 Leading to Death, and TEAEs With Cancer and Leukemia Group B (CALGB) Toxicity Grade 3 or 4 | An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. A serious AE was an AE that results in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with TEAEs, serious TEAEs, TEAEs leading to death, and TEAEs with CALGB toxicity Grade 3 or 4 were reported. | From the first dose of study drug administration until 30 days after the last dose of study drug administration or assessed until cut-off date (15 March 2006) | 
| Overall Survival Time | Time from randomization to death or last day known to be alive. Participants without event were censored at the last date known to be alive or at the clinical cut-off date (15 March 2006), whichever was earlier. | Time from randomization to death or last day known to be alive, reported between day of first participant randomized that is, 08 August 2000, up to cut-off (15 March 2006) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Assessment of Cancer Therapy (FACT-L) Questionnaire Score | Functional Assessment of Cancer Therapy - Lung cancer (FACT-L) is a valid instrument used to measure quality of life (QoL) in participants with cancer consisting of the 27-item FACT-General (G) and 9-item lung cancer subscale (LCS). FACT-G is organized into subscales: physical well-being (PWB)-7 items; social/family well-being (SWB)-7 items; emotional well-being (EWB)-6 items; functional well-being (FWB)-7 items. Each item uses a 5 point rating scale (0=not at all and 4=equals very much). FACT-L total score=4 subscales + LCS and ranges from 0 to 144. Higher scores indicate better QOL. | At baseline, Week 4, Week 8 and then at 12 Week intervals beginning at week 19 until withdrawal/discontinuation from the study. | 
| Number of Participants With Positive T-cell Proliferation | T-cell proliferation assays were performed and the number of participants with positive mucinous glycoprotein 1 (MUC1) specific T-cell proliferative response were reported. | Time from randomization until cut-off date (15 March 2006) | 
| Number of Participants With Elevated CA27-29 Antigen Levels | CA 27-29 is a blood test used to monitor certain types of cancer. CA 27-29 is the name of an antigen, which is a substance that stimulates your body's defense system. CA27-29 antigen levels were determined on all participants and assessed the disease burden of participants at study entry, evaluated early recurrence, presence of residual disease, continued remission or poor prognosis. | Study entry, Week 8 |