Cancer Vaccine Study for Unresectable Stage III Non-small Cell Lung Cancer - Full Text View

Sponsor:	EMD Serono
Collaborator:	Merck KGaA
Information provided by (Responsible Party):	EMD Serono
ClinicalTrials.gov Identifier:	NCT00409188

Purpose

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 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 Stimuvax or placebo vaccination.

Condition	Intervention	Phase
Non-small Cell Lung Cancer	Biological: Stimuvax Biological: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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.

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Cyclophosphamide

U.S. FDA Resources

Further study details as provided by EMD Serono:

Primary Outcome Measures:

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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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) ] [ Designated as safety issue: No ]
Time To Progression (TTP) as determined by the investigator [ Time Frame: Interim analysis at 353 + 529 events (deaths); Final analysis at 705 events (deaths) ] [ Designated as safety issue: No ]
One-, two- and three-year survival [ Time Frame: Analyzed at 1, 2, & 3 years post treatment onset ] [ Designated as safety issue: No ]
Safety [ Time Frame: Assessed throughout, from first patient in until last patient out ] [ Designated as safety issue: Yes ]

Enrollment:	1514
Study Start Date:	December 2006
Estimated Study Completion Date:	September 2014
Estimated Primary Completion Date:	February 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 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 L-BLP25 vaccination. Subjects will then receive eight consecutive weekly subcutaneous vaccinations with L-BLP25 (primary treatment phase) followed by vaccinations with 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])	Biological: Stimuvax A single infusion (IV) of 300mg/m² (to a max.600mg) of Cyclophosphamide will be given three days before first Stimuvax vaccination. Subjects will then receive eight consecutive weekly subcutaneous vaccinations with 806µg of Stimuvax at weeks 0; 1; 2; 3; 4; 5; 6 and 7 followed by maintenance vaccinations (806µg of Stimuvax) at 6-week intervals, commencing at week 13, until disease progression is documented.
Placebo Comparator: 2 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.	Biological: 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.

Arms

Assigned Interventions

Experimental: 1

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 L-BLP25 vaccination. Subjects will then receive eight consecutive weekly subcutaneous vaccinations with L-BLP25 (primary treatment phase) followed by vaccinations with 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])

Biological: Stimuvax

A single infusion (IV) of 300mg/m² (to a max.600mg) of Cyclophosphamide will be given three days before first Stimuvax vaccination.

Subjects will then receive eight consecutive weekly subcutaneous vaccinations with 806µg of Stimuvax at weeks 0; 1; 2; 3; 4; 5; 6 and 7 followed by maintenance vaccinations (806µg of Stimuvax) at 6-week intervals, commencing at week 13, until disease progression is documented.

Placebo Comparator: 2

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.

Biological: 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.

Detailed Description:

Ancillary Trial: An exploratory investigation of immune response in peripheral blood after 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 L-BLP25 (or placebo) vaccination. The main objective is to evaluate whether administration of single-shot, low-dose cyclophosphamide followed by 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 ≥ 100g/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 (80mL whole blood each)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 ECOG performance status of 0-1.
A Platlet count > 140 x 10(9)/L; 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00409188

Show 295 Study Locations

Sponsors and Collaborators

EMD Serono

Merck KGaA

Investigators

Principal Investigator:

Frances Shepherd, MD, FRCPC

Medical Oncology Princess Margaret Hospital, 610 University Avenue, 5-104, Toronto, ON M5G 2M9A, Canada

More Information

Additional Information:

For more information on the study click below This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	EMD Serono
ClinicalTrials.gov Identifier:	NCT00409188 History of Changes
Other Study ID Numbers:	EMR 63325-001
Study First Received:	December 7, 2006
Last Updated:	April 10, 2012
Health Authority:	United States: Food and Drug Administration European Union: European Medicines Agency

Keywords provided by EMD Serono:

Non-Small Cell Lung Carcinoma;
stage III;
unresectable;
vaccine; Stimuvax; L-BLP25;
Cyclophosphamide;

placebo controlled;
randomized;
double blind;
immunotherapy;

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Cyclophosphamide

Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on May 24, 2012