Phase III Lucanix™ Vaccine Therapy in Advanced Non-small Cell Lung Cancer (NSCLC) Following Front-line Chemotherapy

Lung Neoplasm Clinical Trial

— STOP  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00676507
• Other study ID #: NR001-03
• Secondary ID: BB-IND 8868
• Status: Completed
• Phase: Phase 3
• First received: May 8, 2008
• Last updated: May 6, 2015
• Start date: July 2008
• Est. completion date: January 2013

Study information

• Verified date: May 2015
• Source: NovaRx Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardCanada: Health CanadaUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyPoland: Ministry of HealthPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsHungary: National Institute of PharmacySerbia and Montenegro: Agency for Drugs and Medicinal DevicesIndia: Central Drugs Standard Control Organization
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00641966

Recruitment information / eligibility

• Status: Completed
• Enrollment: 532
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma Non-small Cell Lung Cancer Stage IIIA
• Carcinoma Non-small Cell Lung Cancer Stage IIIB
• Carcinoma Non-small Cell Lung Cancer Stage IV
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasm
• Lung Neoplasms

Intervention

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

Other:
• Placebo Comparator
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.

Locations

Country	Name	City	State
Canada	University of Alberta Cross Cancer Institute	Edmonton	Alberta
Canada	Princess Margaret Hospital	Toronto	Ontario
Hungary	Orszagos Koranyi TBC es Pulmonologiai Intezet	Budapest
Hungary	Országos Korányi TBC és Pulmonológiai Intézet	Budapest
Hungary	Semmelweis Egyetem Pulmonológiai Klinika	Budapest
Hungary	Csongrád Megyei Önkormányzat Mellkasi Betegségek Szakkórháza	Deszk
Hungary	Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András Oktató Kórháza	Nyíregyháza
Hungary	Fejér Megyei Szent György Kórház	Székesfehérvár
Hungary	Pest Megyei Tüdogyógyintézet	Törökbálint
India	Gujarat Cancer Hospital and Research Institute	Ahmedabad
India	SEAROC Cancer Center, S.K.	Jaipur
India	Tata Memorial Hospital	Mumbai
India	Noble Hospital	Pune
Netherlands	Ziekenhuis Groep Twente - locatie Twenteborg Ziekenhuis	Almelo
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Antoni van Leeuwenhoek Ziekenhuis	Amsterdam
Netherlands	Universitair Medisch Centrum Maastricht	Maastricht
Poland	Akademickie Centrum Kliniczne Szpital Akademii Medycznej w Gdansku	Gdansk
Poland	Samodzielny Publiczny Szpital Kliniczny nr 4	Lublin
Poland	Wielkopolskie Centrum Pulmunologii i Torakochirurgii	Poznan
Poland	Centrum Onkologii - Instytut im.Marii Sklodowskiej-Curie	Warsaw
Poland	Dolnoslaskie Centrum Chorob Pluc	Wroclaw
Serbia	Klinicko-bolnicki centar Bezanijska kosa	Belgrade
Serbia	Klinicki Centar Nis	Nis
Serbia	Institute for pulmonary disease Sremska Kamenica	Sremska Kamenica
United Kingdom	Clatterbridge Centre for Oncology	Bebington, Wirral
United Kingdom	Ninewells Hospital and Medical School	Dundee
United Kingdom	The Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Guy's Hospital	London
United States	Texas Cancer Center Abilene, Texas Oncology P.A.	Abilene	Texas
United States	Hematology Oncology Life Center	Alexandria	Louisiana
United States	Alaska Regional Hospital	Anchorage	Alaska
United States	Allergy Partners of West North Carolina	Asheville	North Carolina
United States	Cancer Care of WNC	Asheville	North Carolina
United States	University of Colorado Health Science Center	Aurora	Colorado
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	University of Tennessee Cancer Institute	Bartlett	Tennessee
United States	National Cancer Institute Center for Cancer Research, Medical Oncology Branch	Bethesda	Maryland
United States	Eastchester Center for Cancer Care	Bronx	New York
United States	Pasco Hernando Oncology Associates, P.A.	Brooksville	Florida
United States	Gabrail Cancer Center Research LLC	Canton	Ohio
United States	Iowa Blood and Cancer Center	Cedar Rapids	Iowa
United States	Kootenai Cancer Center	Coeur d'Alene	Idaho
United States	Mary Crowley Cancer Research Centers	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Davis Memorial Cancer Care Center	Elkins	West Virginia
United States	University of Tennessee Cancer Institute	Germantown	Tennessee
United States	Cancer Center of the Carolinas	Greenville	South Carolina
United States	Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	St. Francis Medical Group Oncology and Hematology Specialists	Indianapolis	Indiana
United States	Clopton Clinic Hematology/Oncology	Jonesboro	Arkansas
United States	University of California, San Diego	La Jolla	California
United States	Medical Specialist of Palm Beaches	Lake Worth	Florida
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	University of Tennessee Cancer Institute	Memphis	Tennessee
United States	Allison Cancer Center, Texas Oncology, P.A.	Midland	Texas
United States	Optim Oncology	Midwest City	Oklahoma
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Southern Cancer Center	Mobile	Alabama
United States	Ocala Oncology	Ocala	Florida
United States	UCLA Pasadena Oncology	Pasadena	California
United States	Cancer Care Associates	Redondo	California
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Atlanta Cancer Care	Roswell	Georgia
United States	Innovative Research Center of California	San Diego	California
United States	Sansum Clinic	Santa Barbara	California
United States	Santa Barbara Hematology Oncology Medical Group, Inc.	Santa Barbara	California
United States	Central Coast Medical Oncology Corporation	Santa Maria	California
United States	UCLA Cancer Center	Santa Monica	California
United States	Mayo Clinic Cancer Center	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance/Fred Hutchinson Cancer Res Ctr/Univ. of Washington Med Ctr	Seattle	Washington
United States	University of Tennessee Cancer Institute	Southaven	Mississippi
United States	Richmond University Medical Center	Staten Island	New York
United States	Space Coast Medical Center	Titusville	Florida
United States	Tyler Cancer Center, Texas Oncology	Tyler	Texas
United States	UCLA Cancer Center-Valencia	Valencia	California
United States	UCLA Cancer Center	Westlake Village	California
United States	Marshfield Clinic Weston Center	Weston	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
NovaRx Corporation

Countries where clinical trial is conducted

United States,  Canada,  Hungary,  India,  Netherlands,  Poland,  Serbia,  United Kingdom, 

References & Publications (3)

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. Epub 2006 Jul 7. — View 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- — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare the overall survival of subjects with stage III or IV non-small cell lung cancer treated with belagenpumatucel-L (Lucanix™) vs placebo.		7 years	No
Secondary	Evaluate the progression free survival (PFS) of subjects treated with Lucanix™ compared to treatment within the Best Support Care control group.		3 years	No
Secondary	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.		3 years	No
Secondary	Evaluate the time-to-progression of subjects treated with Lucanix™ compared to treatment within the Best Supportive Care control group.		3 years	No
Secondary	Evaluate the best overall tumor response in subjects treated with Lucanix™ compared to treatment in the Best Supportive Care control group.		3 years	No
Secondary	Evaluate the response duration in subjects treated with Lucanix™ compared to the Best Supportive Care control group.		3 years	No
Secondary	Evaluate the rate of CNS metastases development in subjects treated with Lucanix™ as compared to the Best Supportive Care control group.		7 years	No
Secondary	Adverse events of subjects treated with Lucanix™ will be compared to subjects in the Best Supportive Care control group.		7 years	Yes

External Links

•   Main sponsor website