Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000173493
Ethics application status
Approved
Date submitted
6/12/2006
Date registered
19/03/2007
Date last updated
19/05/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
Cancer vaccine study for unresectable stage III non-small cell lung cancer
Scientific 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 to compare the survival duration of all randomized subjects by treatment arm.
Secondary ID [1] 351 0
Merck KGaA: EMR 63325-001
Secondary ID [2] 352 0
ClinicalTrials.gov: NCT00409188
Universal Trial Number (UTN)
Trial acronym
START - Stimulating Targeted Antigenic Responses To NSCLC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small cell lung cancer (NSCLC) subjects with unresectable stage III disease 1688 0
Condition category
Condition code
Cancer 1783 1783 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
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.
Intervention code [1] 1489 0
Treatment: Drugs
Comparator / control treatment
Subjects in the placebo arm will receive 0.9 % sodium chloride (saline) instead of cyclophosphamide and a placebo instead of Stimuvax.
Control group
Placebo

Outcomes
Primary outcome [1] 2491 0
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.
Timepoint [1] 2491 0
The final analysis will take place after the targeted number of events is reached. An independent Data Monitoring Committee will be responsible for periodic evaluations to ensure continued subject safety as well as the validity of the study. In addition, two formal interim analyses are planned.
Once treatment is finished, the subject is contacted every 12 weeks to collect survival data.
Secondary outcome [1] 4296 0
• Time to symptom progression (TTSP) as measured by the Lung Cancer Symptom Scale (LCSS).
Timepoint [1] 4296 0
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] 4297 0
• 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 [2] 4297 0
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] 4298 0
• One-, two- and three-year survival from the date of randomization.
Timepoint [3] 4298 0
One-, two- and three-year survival from the date of randomization.
Secondary outcome [4] 4299 0
• 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 [4] 4299 0
Collected continually until death or the end of the study
Secondary outcome [5] 4300 0
Final analysis.
Timepoint [5] 4300 0
The final analysis will take place after the targeted number of events is reached. An independent Data Monitoring Committee will be responsible for periodic evaluations to ensure continued subject safety as well as the validity of the study. In addition, two formal interim analyses are planned.
Once treatment is finished, the subject is contacted every 12 weeks to collect survival data.

Eligibility
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
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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?



Intervention assignment
Parallel
Other design features
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.
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/12/2006
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
1322
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD,WA
Recruitment outside Australia
Country [1] 441 0
United States of America
State/province [1] 441 0

Funding & Sponsors
Funding source category [1] 1933 0
Commercial sector/Industry
Name [1] 1933 0
Merck KGaA,
Country [1] 1933 0
Germany
Funding source category [2] 1934 0
Commercial sector/Industry
Name [2] 1934 0
EMD Pharmaceuticals Inc.
Country [2] 1934 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Merck KGaA, Darmstadt, Germany
Address
Frankfurter Strasse 25
D-64293 Darmstadt
Country
Germany
Secondary sponsor category [1] 1745 0
Commercial sector/Industry
Name [1] 1745 0
Merck's USA affiliate, EMD Pharmaceuticals Inc., Durham, NC, USA
Address [1] 1745 0
Durham, NC
Country [1] 1745 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 3601 0
Sir Charles Gairdner Hospital
Ethics committee address [1] 3601 0
WA
Ethics committee country [1] 3601 0
Australia
Date submitted for ethics approval [1] 3601 0
Approval date [1] 3601 0
Ethics approval number [1] 3601 0
2006-149
Ethics committee name [2] 3602 0
Austin and Repatriation Medical Centre
Ethics committee address [2] 3602 0
VIC
Ethics committee country [2] 3602 0
Australia
Date submitted for ethics approval [2] 3602 0
Approval date [2] 3602 0
Ethics approval number [2] 3602 0
H2007/02700
Ethics committee name [3] 3603 0
Princess Alexandra Hospital
Ethics committee address [3] 3603 0
QLD
Ethics committee country [3] 3603 0
Australia
Date submitted for ethics approval [3] 3603 0
Approval date [3] 3603 0
Ethics approval number [3] 3603 0
Ethics committee name [4] 3604 0
Royal North Shore Hospital
Ethics committee address [4] 3604 0
NSW
Ethics committee country [4] 3604 0
Australia
Date submitted for ethics approval [4] 3604 0
Approval date [4] 3604 0
Ethics approval number [4] 3604 0
Ethics committee name [5] 3605 0
Royal Prince Alfred Hospital
Ethics committee address [5] 3605 0
NSW
Ethics committee country [5] 3605 0
Australia
Date submitted for ethics approval [5] 3605 0
Approval date [5] 3605 0
Ethics approval number [5] 3605 0
Ethics committee name [6] 4409 0
Sydney West Area Health Service (Nepean Campus)
Ethics committee address [6] 4409 0
NSW
Ethics committee country [6] 4409 0
Australia
Date submitted for ethics approval [6] 4409 0
07/06/2007
Approval date [6] 4409 0
Ethics approval number [6] 4409 0
New application

Summary
Brief summary
This is a study of a cancer vaccine known as Stimuvax for treating non-small cell lung cancer (NSCLC) at stage 3, where this cannot be operated on surgically.

Who is it for?
You may be suitable for this study if:
• You have stage 3 non-small cell lung cancer that cannot be operated on.
• You have received primary platinum chemoradiotherapy.
• The cancer is stable or responsive.

Trial details
Participants will be randomly divided into two groups. Four weeks after the last chemoradiation treatment, one group receives one infusion of cyclophosphamide followed by weekly subcutaneous vaccination with Stimuvax for 8 weeks and then injections are given once every six weeks until any progression of the cancer. The other group will receive a non-active compound. The study aims to monitor survival time and time to any progression of symptoms.

Currently there is no standard prescribed treatment for these people following chemoradiotherapy. Stimuvax is designed to stimulate the immune system to respond to a protein found in many cancers including NSCLC. This trial will determine if Stimuvax has beneficial effects after participants cease chemoradiation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27423 0
Address 27423 0
Country 27423 0
Phone 27423 0
Fax 27423 0
Email 27423 0
Contact person for public queries
Name 10678 0
A/Prof Paul Mitchell
Address 10678 0
Cancer Services Administration
Level D
3KZ Building
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 10678 0
Australia
Phone 10678 0
+61 3 94963546
Fax 10678 0
+61 3 94963379
Email 10678 0
Paul.MITCHELL@austin.org.au
Contact person for scientific queries
Name 1606 0
A/Prof Paul Mitchell
Address 1606 0
Cancer Services Administration
Level D
3KZ Building
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 1606 0
Australia
Phone 1606 0
+61 3 94963546
Fax 1606 0
+61 3 94963379
Email 1606 0
Paul.MITCHELL@austin.org.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.