Cancer Vaccine Study for Unresectable Stage III Non-small Cell Lung Cancer (START)
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Tecemotide (L-BLP25); Single low dose cyclophosphamide; Placebo
Intervention description: After receiving cyclophosphamide, participants will receive 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 is documented.; 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 first tecemotide (L-BLP25) vaccination.; 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.
Intervention MeSH terms: Cyclophosphamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1513.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Small Cell Lung Carcinoma;; stage III;; unresectable;; vaccine; Tecemotide; L-BLP25;; Cyclophosphamide;; placebo controlled;; randomized;; double blind;; immunotherapy;

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 subjects 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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically documented unresectable stage III non-small cell lung
             cancer (NSCLC)

          -  Documented stable disease or objective response, according to Response Evaluation
             Criteria in Solid Tumors (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 Gray (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/Liter; white blood cells (WBC) > 2.5 x 10^9/Liter and
             hemoglobin > 90 gram per liter (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