Official Title: “A Multi-national, Double-blind, Placebo-controlled, Randomized, Phase III Clinical Trial of the Cancer Vaccine Stimuvax® (L-BLP25 or BLP25 Liposome Vaccine) in Asian Subjects With Stage III, Unresectable, Non-small Cell Lung Cancer (NSCLC) Who Have Demonstrated Either Stable Disease or Objective Response Following Primary Chemo-radiotherapy”

The purpose of this study is to determine whether the cancer vaccine Stimuvax in addition to best supportive care is effective in prolonging the lives of Asian patients with unresectable stage III non-small cell lung cancer in comparison to a placebo plus best supportive care (a so-called Placebo controlled study).

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: September 2014

Intervention(s) in this Clinical Trial

• Biological: L-BLP25 or BLP25 liposome vaccine (Stimuvax)
  • All subjects randomized to the investigational arm will begin the following treatment regimen within three days of randomization: A single I.V. infusion of 300 mg/m2 of cyclophosphamide administered exactly three days prior to the first L-BLP25 (Stimuvax) vaccination. Subjects will then receive eight consecutive weekly subcutaneous vaccinations with 1000 μg BLP25 lipopeptide (Stimuvax) at weeks 1, 2, 3, 4, 5, 6, 7, and 8 (primary treatment phase) and then at six-week intervals, beginning at week 14 (maintenance phase) and continuing until disease progression is documented or the subject discontinues for any other reason.
• Biological: Placebo
  • A single I.V. infusion of 0.9% sodium chloride will be administered to subjects randomized to the control arm exactly 3 days prior to treatment with placebo. Subjects will then receive eight consecutive weekly subcutaneous treatments with placebo at weeks 1, 2, 3, 4, 5, 6, 7, and 8 followed by maintenance treatment at 6 week intervals, beginning at week 14 and continuing until disease progression is documented.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Investigational Arm
  • Pretreatment (Single Dose): 300 mg/m2 of IV cyclophosphamide L-BLP25 plus Best Supportive Care (BSC)
• Placebo Comparator: Control Arm
  • Pretreatment (Single Dose): 0.9% sodium chloride infusion Placebo plus BSC

Primary Measures

• The primary variable of this trial is overall survival time. It will be measured from the date of randomization to the date of death.
  • Time Frame: various timepoints
    Safety Issue?: No

Secondary Measures

• Safety
  • Time Frame: various timepoints
    Safety Issue?: No

Inclusion Criteria:

• Histologically or cytologically documented unresectable stage III NSCLC.
• Documented stable disease or objective response, according to RECIST after primary chemo-radiotherapy (either sequential or concomitant) for unresectable stage III disease, within four weeks (28 days) prior to randomization.
• Receipt of concomitant or sequential chemo-radiotherapy, 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 or 1
• A platelet count ≥ 100 x 10 to the 9th power/L; WBC ≥ 2.5 x 109/L and hemoglobin ≥ 90 g/L
• ≥18 years of age (or minimum age of legal consent consistent with local regulations, if minimum is > 18 years of age)

Exclusion Criteria:

Pre-Therapies*:

• Lung-cancer-specific therapy (including surgery) other than primary chemoradiotherapy.
• Immunotherapy (e.g., interferons, tumor necrosis factor [TNF], interleukins, or biological response modifiers [granulocyte macrophage colony stimulating factor
• {GMCSF}, granulocyte colony stimulating factor {G-CSF}, macrophage-colony stimulating factor {M-CSF}], monoclonal antibodies) within four weeks (28 days) prior to randomization.
• Investigational systemic drugs (including off-label use of approved products) within four weeks (28 days) prior to randomization.

Disease Status:

• Metastatic disease
• Malignant pleural effusion at initial diagnosis and/or at trial 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 that in the opinion of the investigator could compromise the safety of the subject in this trial
• 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 active Hepatitis B infection and/or Hepatitis C infection
• Signs and symptoms suggestive of transmissible spongiform encephalopathy, or of family members who suffer(ed) from such

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 breastfeeding women, women of childbearing potential, unless using effective contraception as determined by the investigator.
• Known drug abuse or alcohol abuse
• Participation in another clinical trial within the past 28 days
• Requires concurrent treatment with a non-permitted drug
• Known hypersensitivity to any of the trial treatment ingredients
• Legal incapacity or limited legal capacity

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: EMD Serono

Overall Clinical Trial Officials and Contacts

Nassim Morsli, MD Study Director Merck KGaA  

Overall Contact: Merck KGaA Communication Center +49 6151 72 5200 service@merck.de

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01015443

Study ID Number: EMR63325-012

ClinicalTrials.gov Identifier: NCT01015443

Health Authority: China: Ministry of Health