Detailed Description of START Trial
(from a secret source!!)
Cancer vaccine study for unresectable stage III non-small cell lung cancer
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 to compare the survival duration of all randomized subjects by treatment arm.
Brief summary: Currently, there are no recommended treatment options for patients with unresectable stage III non-small cell lung cancer who are stable or responding following chemo-radiotherapy. Stimuvax is a therapeutic cancer vaccine that is designed to stimulate the immune system to respond to a specific protein found in many common cancers, including non-small cell lung cancer (NSCLC). Stimuvax is thought to work by stimulating the body’s immune system to identify and destroy these specific cancer cells.
Secondary ID 1: Merck KGaA: EMR 63325-001
Secondary ID 2: ClinicalTrials.gov: NCT00409188
Trial acronym: START - Stimulating Targeted Antigenic Responses To NSCLC
Health condition(s) or problem(s) studied:
Non-small cell lung cancer (NSCLC) subjects with unresectable stage III disease
Description of intervention(s) / exposure:
Investigational arm:
Pre-treatment: one intravenous infusion of cyclophosphamide (infusion of 300 mg/m2, determined by calculation of the subject's body surface area. A maximum dose of 600mg will be given).
Primary treatment: weekly subcutaneous vaccinations with Stimuvax (subcutaneous injection of 1,000 µg) for 8 consecutive weeks. Maintenance treatment: vaccinations with Stimuvax (subcutaneous injection of 1,000 µg) at 6-week intervals. Subjects will be discontinued upon documented disease progression.
Comparator / control treatment:
Subjects in the placebo arm will receive 0.9 % sodium chloride (saline) instead of cyclophosphamide and a placebo instead of Stimuvax.
Primary outcome:
The primary variable of this study is the survival duration. Survival will be measured as the number of months between the date of randomization and the date of death.
The final analysis will take place after the targeted number of events (705 deaths) is reached, which is estimated to take place 48 months post study initiation. Two formal interim analysis are also planned. Once treatment is finished, the subject is contacted every 12 weeks to collect survival data. An independent Data Monitoring Committee will be responsible for periodic evaluations to ensure continued subject safety as well as the validity of the study.
Secondary outcome 1: • Time to symptom progression (TTSP) as measured by the Lung Cancer Symptom Scale (LCSS).
Timepoint: Completed every 3 weeks during the primary treatment phase, every 6 weeks during the maintenance treatment and every 12 weeks during the follow up period.
Secondary outcome 2: • Time to progression (TTP) as determined by the investigator during scheduled visits every week in the primary treatment phase, every 6 weeks during the maintenance treatment phase and at ad-hoc routine site visits.
Timepoint: For each patient it is measured every week in the primary treatment phase, every 6 weeks during the maintenance treatment phase and at ad-hoc routine site visits
Secondary outcome 3: • One-, two- and three-year survival from the date of randomization.
Timepoint: One-, two- and three-year survival from the date of randomization.
Secondary outcome 4: • Safety. Safety data are collected on a continual basis up until the end of treatment. Any events considered related to study drug are followed until resolution.
Timepoint: Collected continually until death or the end of the study.
Key inclusion criteria: Histologically or cytologically documented unresectable stage III NSCLC. -Documented stable disease or objective response, according to Response Evaluation Criteria in Solid Tumors (RECIST), after primary chemo-radiotherapy (either sequential or concomitant) for unresectable stage III disease, within 4 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 ECOG (The Eastern Cooperative Oncology Group) performance status of 0-1.
Minimum Age: 18 Years
Maximum Age: Not stated
Gender: Both males and females
Key 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 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 that in the opinion of the investigator could compromise the safety of the subject in this study. -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
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures): Central randomization by Interactive Voice Response System (IVRS)
Methods used to generate the sequence in which subjects will be randomised (sequence generation): Randomization will be determined by Computer Generated Stratified Randomization List. Treatment is assigned from a strata specific list. Stratification factors are: Geographical Region (EU west; {USA, Canada and Australia}; Rest of World); Disease Stage (stage IIIA or IIIB); Type of Primary Chemo-Radiotherapy (concomitant or sequential); Response to Primary Treatment (objective response or stable disease).There are 2 treatment groups.
Approximate treatment ratio: 2 / 1 (Active / Placebo)
Masking / blinding: Blinded (masking used)
Who is/are masked/blinded:
The people receiving the treatment/s
The people administering the treatment/s
Assignment: Parallel
Other design features (specify): The patient, the investigator and his research team treating the patient and any data managers at site will be blinded. Pharmacist(s) on site, however, will be unblinded to the treatment arms as the cyclophosphamide is open label. Medication will be blinded before it is provided to the person administering. The sponsor and representatives of the sponsor will be blinded. However, an unblinded monitor will be assigned to perform the drug accountability. Appointed personnel from PRA and Merck will be unblinded so that safety reports from site can be reviewed.
Approximate start date: 15/02/2007
Target sample size: 1322
Recruitment status: Open to recruitment
Primary sponsor: Commercial sector/Industry
Name: Merck KGaA, Darmstadt, Germany
