Overview

This trial is active, not recruiting.

Condition non-small cell lung cancer
Treatments tecemotide (l-blp25), placebo
Phase phase 3
Sponsor EMD Serono
Collaborator Merck KGaA
Start date January 2007
End date August 2012
Trial size 1513 participants
Trial identifier NCT00409188, EMR 63325-001

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 patients 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Following randomization, subjects in the investigational arm will receive, within 3 days of their treatment assignment, a single intravenous (I.V.) infusion of 300 mg/m2 (to a maximum of 600 mg) cyclophosphamide three days before the first Tecemotide (L-BLP25) vaccination. Subjects will then receive eight consecutive weekly subcutaneous vaccinations with Tecemotide (L-BLP25) (primary treatment phase) followed by vaccinations with Tecemotide (L-BLP25) at 6-week intervals, commencing at week 13 (maintenance treatment phase). Subjects will be discontinued from the study treatment upon documented disease progression (to be assessed according to Response Evaluation Criteria in Solid Tumors [RECIST]).
tecemotide (l-blp25)
A single infusion (IV) of 300mg/m² (to a max.600mg) of Cyclophosphamide will be given three days before first L-BLP25 vaccination. Subjects will then receive eight consecutive weekly subcutaneous vaccinations with 806µg of Tecemotide (L-BLP25) at weeks 0; 1; 2; 3; 4; 5; 6 and 7 followed by maintenance vaccinations (806µg of Tecemotide (L-BLP25) at 6-week intervals, commencing at week 13, until disease progression is documented.
(Placebo Comparator)
Following randomization, subjects in the placebo arm will receive, within 3 days of their treatment assignment, 0.9 percent (%) sodium chloride (saline) instead of cyclophosphamide and placebo instead of L-BLP25.
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.

Primary Outcomes

Measure
To compare survival duration of all randomized subjects by treatment arm
time frame: Interim analysis at 353 + 529 events (deaths); Final analysis at 705 events (deaths)

Secondary Outcomes

Measure
To compare all randomized subjects by treatment arm for: Time To Symptom Progression (TTSP) as measured by the Lung Cancer Symptom Scale (LCSS)
time frame: Interim analysis at 353 + 529 events (deaths); Final analysis at 705 events (deaths)
Time To Progression (TTP) as determined by the investigator
time frame: Interim analysis at 353 + 529 events (deaths); Final analysis at 705 events (deaths)
One-, two- and three-year survival
time frame: Analyzed at 1, 2, & 3 years post treatment onset
Safety
time frame: Assessed throughout, from first patient in until last patient out

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically or cytologically documented unresectable stage III NSCLC - Documented stable disease or objective response, according to 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 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)/L; white blood cells (WBC) > 2.5 x 10(9)/L and hemoglobin > 90 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

Additional Information

Official title 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.
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 a 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 as well as a modulation of cellular and soluble components of the immune response in patients 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 patients All inclusion criteria specified in the START clinical trial protocol except for hemoglobin >= 100 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 mL whole blood each)
Trial information was received from ClinicalTrials.gov and was last updated in October 2014.
Information provided to ClinicalTrials.gov by EMD Serono.