Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
Conditions
Keywords
Carcinoma, Non-Small-Cell Lung, L-BLP25, Tecemotide
Brief summary
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.
Interventions
BIOLOGICALTecemotide (L-BLP25)
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.
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.
OTHERBest standard of care (BSC)
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.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Up to data cut-off date (17 September 2007) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival Time | Up to data cut-off date (17 September 2007) | 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. |
| Progression Free Survival (PFS) Time | Up to data cut-off date (17 September 2007) | 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. |
Participant flow
Recruitment details
First/last participant (informed consent): April 2005/September 2005. Last participant completed: April 2012; Clinical data cut-off: 17 September 2007. The study was conducted at 8 centers in Canada.
Pre-assignment details
Enrolled: 22 participants.
Participants by arm
| Arm | Count |
|---|---|
| Tecemotide (L-BLP25)+Cyclophosphamide+Best Standard of Care A single intravenous infusion of 300 mg/m\^2 (to a maximum 600 mg) of cyclophosphamide was administered 3 days prior to tecemotide (L-BLP25) first vaccine treatment followed by weekly subcutaneous vaccinations of 1000 mcg of tecemotide (L-BLP25) at Week 0, 1, 2, 3, 4, 5, 6, and 7 in the primary treatment phase. Maintenance dose of 1000 mcg of tecemotide (L-BLP25) was administered subcutaneously in the deltoid or triceps region of the upper arms, and the left and right anterolateral aspects of the abdomen at a 6-week intervals, starting at Week 13, until disease progression was documented. The BSC was provided at the investigator's discretion, and included psychosocial support, nutritional support and other supportive therapies as required. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ongoing at data cut-off | 9 |
Baseline characteristics
| Characteristic | Tecemotide (L-BLP25)+Cyclophosphamide+Best Standard of Care |
|---|---|
| Age, Continuous | 58.2 years STANDARD_DEVIATION 9.66 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 22 |
| serious Total, serious adverse events | 4 / 22 |
Outcome results
Primary
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.
Time frame: Up to data cut-off date (17 September 2007)
Population: Safety analysis set included all the enrolled participants who received at least one dose of the trial treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tecemotide (L-BLP25)+Cyclophosphamide+Best Standard of Care | 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) | Serious TEAEs | 4 participants |
| Tecemotide (L-BLP25)+Cyclophosphamide+Best Standard of Care | 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 with CALGB-ECTC Grade 3 or 4 | 13 participants |
| Tecemotide (L-BLP25)+Cyclophosphamide+Best Standard of Care | 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 leading to death | 1 participants |
| Tecemotide (L-BLP25)+Cyclophosphamide+Best Standard of Care | 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) | ISRs | 11 participants |
| Tecemotide (L-BLP25)+Cyclophosphamide+Best Standard of Care | 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 | 22 participants |
Secondary
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.
Time frame: Up to data cut-off date (17 September 2007)
Population: Safety analysis set included all the enrolled participants who received at least one dose of the trial treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tecemotide (L-BLP25)+Cyclophosphamide+Best Standard of Care | Progression Free Survival (PFS) Time | NA months |
Secondary
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.
Time frame: Up to data cut-off date (17 September 2007)
Population: Safety analysis set included all the enrolled participants who received at least one dose of the trial treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tecemotide (L-BLP25)+Cyclophosphamide+Best Standard of Care | Survival Time | NA months |