Clinical trial NCT00676507: Phase III Lucanix™ Vaccine Therapy in Advanced Non-small Cell Lung Cancer (NSCLC) Following Front-line Chemotherapy
Official title: Phase III Study of Lucanix™ (Belagenpumatucel-L) in Advanced Non-small Cell Lung Cancer: An International Multicenter, Randomized, Double-blinded, Placebo-controlled Study of Lucanix™ Maintenance Therapy for Stages III/IV NSCLC Subjects Who Have Responded to or Have Stable Disease Following One Regimen of Front-line, Platinum-based Combination Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Neoplasm
Carcinoma Non-small Cell Lung Cancer Stage IIIA
Carcinoma Non-small Cell Lung Cancer Stage IIIB
Carcinoma Non-small Cell Lung Cancer Stage IV
Keywords: Gene therapy
Flow cytometry
Immunoenzyme technique
Laboratory biomarker analysis
Quality-of-life-assessment
Tumor cell-derivative vaccine therapy
Lead sponsor: NovaRx Corporation
Sponsor class: INDUSTRY
First posted: 2008-05-13
Enrollment: 532
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Rationale: Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells. It is not yet known whether vaccine therapy is more effective than a placebo as maintenance therapy in treatment of subjects with non-small cell lung cancer.

Purpose: This randomized phase III trial is studying vaccine therapy to see how well it works compared with a placebo in treating subjects with stage III or stage IV non-small cell lung cancer.

Detailed description: Primary Efficacy Endpoints:

* Compare the overall survival of subjects with stage III or IV non-small cell lung cancer treated with belagenpumatucel-L (Lucanix™) vs placebo.

Secondary Efficacy Endpoints:

* Evaluate the progression free survival (PFS) of subjects treated with Lucanix™ compared to treatment within the BSC control group.
* Evaluate the quality of life (QOL) as determined by the Lung Cancer Symptom Scale (LCSS) compared to treatment within the BSC control group.
* Evaluate the time-to-progression of subjects treated with Lucanix™ compared to treatment within the BSC control group.
* Evaluate the best overall tumor response in subjects treated with Lucanix™ compared to treatment in the BSC control group.
* Evaluate the response duration in subjects treated with Lucanix™ compared to the BSC control group.
* Evaluate the rate of CNS metastases development in subjects treated with Lucanix™ as compared to the BSC control group.
* Adverse events of subjects treated with Lucanix™ will be compared to subjects in the control group.

Outline: This is a multicenter study. Subjects are stratified according to disease stage (IIIA vs IIIB or IV), response to prior treatment with front-line chemotherapy (stable disease vs partial response or complete response), prior treatment with front-line chemotherapy and radiotherapy (front-line chemotherapy with radiotherapy vs front-line chemotherapy alone), and prior treatment with front-line chemotherapy and other anticancer therapy (front-line chemotherapy with bevacizumab vs front-line chemotherapy alone or in combination with another anticancer agent). Subjects are randomized to 1 of 2 treatment arms.

* Treatment Arm: Subjects receive belagenpumatucel-L (Lucanix™) intradermally (ID) once monthly for 18 months and then once at 21 and 24 months in the absence of disease progression or unacceptable toxicity.
* Control Arm: Subjects receive placebo ID once monthly for 18 months and then once at 21 and 24 months in the absence of disease progression or unacceptable toxicity.

Blood samples are collected and analyzed for routine chemistry, cytokines, chemokines, and some instances circulating tumor cells, including response to multiple lung cancer-associated antigens by IFN-γ ELISPOT CD8+ assay; CEA by CD4 class II assay; lung tumor-associated antigens by in vitro proliferation assays; regulatory T-cell (Treg) phenotype by flow cytometry; and Treg function.

Subjects complete the Lung Cancer Symptom Scale quality of life questionnaire at baseline, on the days of treatment, 30 days after completion of study treatment, and then every 3 months for 1 year.

After completion of study treatment, subjects are followed every 3 months for 1 year and then annually for 4 years.

In two phase II trials, many subjects who received Lucanix™ at the same dose that will be administered in this trial had long-term disease stability with a good quality of life.

Eligibility criteria: Inclusion Criteria:

* Subjects with histologically or cytologically confirmed NSCLC who meet one of the following staging requirements:
* Stage IIIA (T3N2 only) or
* Stage IIIB or
* Stage IV.
* Subjects must have stable disease (SD) or an objective response (PR or CR) to a prior single, frontline, platinum-based chemotherapy regimen (additional prior adjuvant chemotherapy is permitted) consisting of up to six (6) treatment cycles with or without concomitant radiation therapy.
* Not less than four weeks nor more than four months must have elapsed since the completion of the last chemotherapy cycle and registration into the study.
* Subjects treated for brain metastasis(es) are eligible if they have been stable for ≥ 2 months.
* Signed informed consent.
* Not less than 18 years and not more than 75 years old.
* Estimated life expectancy of at least 12 weeks.
* Performance status (ECOG) ≤ 2.
* Absolute neutrophil count ≥ 1,500/mm3.
* Hemoglobin ≥ 9 g/dL.
* Platelet count ≥ 100,000/mm3.
* Albumin levels ≥ 2.5 g/dL.
* Bilirubin ≤ 1.5 times the upper limit of normal (ULN).
* Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 1.5 × ULN.
* Creatinine ≤ 1.5 × ULN.
* Alkaline phosphatase ≤ 5 × ULN.

Exclusion Criteria:

* Concurrent systemic steroids \> 2 mg /day prednisone (or prednisone-equivalent of prednisolone or dexamethasone).
* Prior splenectomy.
* Any surgery involving general anesthesia \< 4 weeks prior to study registration.
* Chemotherapy more than 4 months or less than 4 weeks prior to study registration.
* Steroid therapy (excluding ≤ 2 mg/day prednisone or prednisone-equivalent of prednisolone or dexamethasone), radiation therapy, or immunotherapy less than 4 weeks prior to study registration.
* Subjects with documented active brain metastasis(es) at the time of study entry are ineligible. However, subjects treated for brain metastasis(es) are eligible if they have been stable for ≥ 2 months.
* Painful bone metastases, or bone metastases that require immediate therapy.
* Significant and/or symptomatic pleural effusions. Presence of clinically detectable (by physical exam) third-space fluid collections, for example, pleural effusions that cannot be controlled by previous chemotherapy and/or drainage, or other procedures, prior to study entry.
* Known allergies to eggs or soy.
* Significant weight loss (≥ 10% body weight in preceding 6 weeks).
* Known HIV positivity (EBV origin of replication in the pCHEK/HBA2 vector used to modify the vaccine components can trans-activate HIV).
* Serious non-malignant disease (e.g., congestive heart failure, or active uncontrolled bacterial, viral, or fungal infections) or other conditions that, in the opinion of the investigator, would compromise study objectives.
* NCI CTC Grade 3 or 4 peripheral neuropathy at study registration.
* Prior other malignancies (excluding non-melanoma carcinomas of the skin) unless in remission for ≥ 2 years.
* History of psychiatric disorder that would impede ability to give informed consent or adherence to study requirements.
* Pregnant or nursing women, or refusal to practice contraception if of reproductive potential.
* Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
* Known active Epstein-Barr infection within ≤ 60 days of study registration.

Primary outcomes:
measure: Compare the overall survival of subjects with stage III or IV non-small cell lung cancer treated with belagenpumatucel-L (Lucanix™) vs placebo.
timeFrame: 7 years
Secondary outcomes:
measure: Evaluate the progression free survival (PFS) of subjects treated with Lucanix™ compared to treatment within the Best Support Care control group.
timeFrame: 3 years
measure: Evaluate the quality of life (QOL) as determined by the Lung Cancer Symptom Scale (LCSS) compared to treatment within the Best Supportive Care control group.
timeFrame: 3 years
measure: Evaluate the time-to-progression of subjects treated with Lucanix™ compared to treatment within the Best Supportive Care control group.
timeFrame: 3 years
measure: Evaluate the best overall tumor response in subjects treated with Lucanix™ compared to treatment in the Best Supportive Care control group.
timeFrame: 3 years
measure: Evaluate the response duration in subjects treated with Lucanix™ compared to the Best Supportive Care control group.
timeFrame: 3 years
measure: Evaluate the rate of CNS metastases development in subjects treated with Lucanix™ as compared to the Best Supportive Care control group.
timeFrame: 7 years
measure: Adverse events of subjects treated with Lucanix™ will be compared to subjects in the Best Supportive Care control group.
timeFrame: 7 years
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Southern Cancer Center
state: Alabama
city: Anchorage
country: United States
facility: Alaska Regional Hospital
state: Alaska
city: Scottsdale
country: United States
facility: Mayo Clinic Cancer Center
state: Arizona
city: Jonesboro
country: United States
facility: Clopton Clinic Hematology/Oncology
state: Arkansas
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Pasadena
country: United States
facility: UCLA Pasadena Oncology
state: California
city: Redondo
country: United States
facility: Cancer Care Associates
state: California
city: San Diego
country: United States
facility: Innovative Research Center of California
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Hematology Oncology Medical Group, Inc.
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Santa Monica
country: United States
facility: UCLA Cancer Center
state: California
city: Valencia
country: United States
facility: UCLA Cancer Center-Valencia
state: California
city: Westlake Village
country: United States
facility: UCLA Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Health Science Center
state: Colorado
city: Brooksville
country: United States
facility: Pasco Hernando Oncology Associates, P.A.
state: Florida
city: Lake Worth
country: United States
facility: Medical Specialist of Palm Beaches
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology
state: Florida
city: Titusville
country: United States
facility: Space Coast Medical Center
state: Florida
city: Roswell
country: United States
facility: Atlanta Cancer Care
state: Georgia
city: Coeur d'Alene
country: United States
facility: Kootenai Cancer Center
state: Idaho
city: Indianapolis
country: United States
facility: St. Francis Medical Group Oncology and Hematology Specialists
state: Indiana
city: Cedar Rapids
country: United States
facility: Iowa Blood and Cancer Center
state: Iowa
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
city: Alexandria
country: United States
facility: Hematology Oncology Life Center
state: Louisiana
city: Bethesda
country: United States
facility: National Cancer Institute Center for Cancer Research, Medical Oncology Branch
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Southaven
country: United States
facility: University of Tennessee Cancer Institute
state: Mississippi
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Hackensack
country: United States
facility: Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Eastchester Center for Cancer Care
state: New York
city: Staten Island
country: United States
facility: Richmond University Medical Center
state: New York
city: Asheville
country: United States
facility: Allergy Partners of West North Carolina
state: North Carolina
city: Asheville
country: United States
facility: Cancer Care of WNC
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center Research LLC
state: Ohio
city: Midwest City
country: United States
facility: Optim Oncology
state: Oklahoma
city: Greenville
country: United States
facility: Cancer Center of the Carolinas
state: South Carolina
city: Bartlett
country: United States
facility: University of Tennessee Cancer Institute
state: Tennessee
city: Germantown
country: United States
facility: University of Tennessee Cancer Institute
state: Tennessee
city: Memphis
country: United States
facility: University of Tennessee Cancer Institute
state: Tennessee
city: Abilene
country: United States
facility: Texas Cancer Center Abilene, Texas Oncology P.A.
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Centers
state: Texas
city: Midland
country: United States
facility: Allison Cancer Center, Texas Oncology, P.A.
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center, Texas Oncology
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance/Fred Hutchinson Cancer Res Ctr/Univ. of Washington Med Ctr
state: Washington
city: Elkins
country: United States
facility: Davis Memorial Cancer Care Center
state: West Virginia
city: Weston
country: United States
facility: Marshfield Clinic Weston Center
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Budapest
country: Hungary
facility: Orszagos Koranyi TBC es Pulmonologiai Intezet
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Pulmonológiai Klinika
city: Budapest
country: Hungary
facility: Országos Korányi TBC és Pulmonológiai Intézet
city: Deszk
country: Hungary
facility: Csongrád Megyei Önkormányzat Mellkasi Betegségek Szakkórháza
city: Nyíregyháza
country: Hungary
facility: Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András Oktató Kórháza
city: Székesfehérvár
country: Hungary
facility: Fejér Megyei Szent György Kórház
city: Törökbálint
country: Hungary
facility: Pest Megyei Tüdőgyógyintézet
city: Ahmedabad
country: India
facility: Gujarat Cancer Hospital and Research Institute
city: Jaipur
country: India
facility: SEAROC Cancer Center, S.K.
city: Mumbai
country: India
facility: Tata Memorial Hospital
city: Pune
country: India
facility: Noble Hospital
city: Almelo
country: Netherlands
facility: Ziekenhuis Groep Twente - locatie Twenteborg Ziekenhuis
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis
city: Maastricht
country: Netherlands
facility: Universitair Medisch Centrum Maastricht
city: Gdansk
country: Poland
facility: Akademickie Centrum Kliniczne Szpital Akademii Medycznej w Gdansku
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 4
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Pulmunologii i Torakochirurgii
city: Warsaw
country: Poland
facility: Centrum Onkologii - Instytut im.Marii Sklodowskiej-Curie
city: Wroclaw
country: Poland
facility: Dolnoslaskie Centrum Chorob Pluc
city: Belgrade
country: Serbia
facility: Klinicko-bolnicki centar Bezanijska kosa
city: Nis
country: Serbia
facility: Klinicki Centar Nis
city: Sremska Kamenica
country: Serbia
facility: Institute for pulmonary disease Sremska Kamenica
city: Bebington, Wirral
country: United Kingdom
facility: Clatterbridge Centre for Oncology
city: Dundee
country: United Kingdom
facility: Ninewells Hospital and Medical School
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Guy's Hospital
Study officials:
References:
citation: Fakhrai H, Mantil JC, Liu L, Nicholson GL, Murphy-Satter CS, Ruppert J, Shawler DL. Phase I clinical trial of a TGF-beta antisense-modified tumor cell vaccine in patients with advanced glioma. Cancer Gene Ther. 2006 Dec;13(12):1052-60. doi: 10.1038/sj.cgt.7700975. Epub 2006 Jul 7.
citation: Nemunaitis J, Nemunaitis M, Senzer N, Snitz P, Bedell C, Kumar P, Pappen B, Maples PB, Shawler D, Fakhrai H. Phase II trial of Belagenpumatucel-L, a TGF-beta2 antisense gene modified allogeneic tumor vaccine in advanced non small cell lung cancer (NSCLC) patients. Cancer Gene Ther. 2009 Aug;16(8):620-4. doi: 10.1038/cgt.2009.15. Epub 2009 Mar 13.
citation: Nemunaitis J, Dillman RO, Schwarzenberger PO, Senzer N, Cunningham C, Cutler J, Tong A, Kumar P, Pappen B, Hamilton C, DeVol E, Maples PB, Liu L, Chamberlin T, Shawler DL, Fakhrai H. Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer. J Clin Oncol. 2006 Oct 10;24(29):4721-30. doi: 10.1200/JCO.2005.05.5335. Epub 2006 Sep 11.
citation: Giaccone G, Bazhenova LA, Nemunaitis J, Tan M, Juhasz E, Ramlau R, van den Heuvel MM, Lal R, Kloecker GH, Eaton KD, Chu Q, Dunlop DJ, Jain M, Garon EB, Davis CS, Carrier E, Moses SC, Shawler DL, Fakhrai H. A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer. Eur J Cancer. 2015 Nov;51(16):2321-9. doi: 10.1016/j.ejca.2015.07.035. Epub 2015 Aug 14.