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

NCT ID: NCT00676507

Last Updated: 2015-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 532 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2013-01-31

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Treatment

Treatment Arm: This course of therapy is Best Support Care (BSC) plus monthly intradermal (ID) injections of Lucanix™ (belagenpumatucel-L) consisting of 25,000,000 cells in a volume of 0.40 mL.

Group Type: EXPERIMENTAL

Lucanix™

Intervention Type: BIOLOGICAL

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.

Control Arm

Control Arm: This course of therapy is Best Support Care (BSC) plus a placebo injection that consists of 0.15% Intralipid® in solution composed of the cryopreservation formulation minus the gene modified cells and dimethyl sulfoxide (DMSO) in a volume of 0.40 mL.

Group Type: PLACEBO_COMPARATOR

Placebo Comparator

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: BIOLOGICAL

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.

Intervention Type: OTHER

Other Intervention Names

belagenpumatucel-L

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NovaRx Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Samodzielny Publiczny Szpital Kliniczny nr 4

Lublin, , Poland

Southern Cancer Center

Mobile, Alabama, United States

Alaska Regional Hospital

Anchorage, Alaska, United States

Mayo Clinic Cancer Center

Scottsdale, Arizona, United States

Clopton Clinic Hematology/Oncology

Jonesboro, Arkansas, United States

Comprehensive Blood and Cancer Center

Bakersfield, California, United States

University of California, San Diego

La Jolla, California, United States

UCLA Pasadena Oncology

Pasadena, California, United States

Cancer Care Associates

Redondo, California, 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

UCLA Cancer Center-Valencia

Valencia, California, United States

UCLA Cancer Center

Westlake Village, California, United States

University of Colorado Health Science Center

Aurora, Colorado, United States

Pasco Hernando Oncology Associates, P.A.

Brooksville, Florida, United States

Medical Specialist of Palm Beaches

Lake Worth, Florida, United States

Ocala Oncology

Ocala, Florida, United States

Space Coast Medical Center

Titusville, Florida, United States

Atlanta Cancer Care

Roswell, Georgia, United States

Kootenai Cancer Center

Coeur d'Alene, Idaho, United States

St. Francis Medical Group Oncology and Hematology Specialists

Indianapolis, Indiana, United States

Iowa Blood and Cancer Center

Cedar Rapids, Iowa, United States

James Graham Brown Cancer Center

Louisville, Kentucky, United States

Hematology Oncology Life Center

Alexandria, Louisiana, United States

National Cancer Institute Center for Cancer Research, Medical Oncology Branch

Bethesda, Maryland, United States

Henry Ford Health System

Detroit, Michigan, United States

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

University of Tennessee Cancer Institute

Southaven, Mississippi, United States

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Richmond University Medical Center

Staten Island, New York, United States

Eastchester Center for Cancer Care

The Bronx, New York, United States

Allergy Partners of West North Carolina

Asheville, North Carolina, United States

Cancer Care of WNC

Asheville, North Carolina, United States

Gabrail Cancer Center Research LLC

Canton, Ohio, United States

Optim Oncology

Midwest City, Oklahoma, United States

Cancer Center of the Carolinas

Greenville, South Carolina, United States

University of Tennessee Cancer Institute

Bartlett, Tennessee, United States

University of Tennessee Cancer Institute

Germantown, Tennessee, United States

University of Tennessee Cancer Institute

Memphis, Tennessee, United States

Texas Cancer Center Abilene, Texas Oncology P.A.

Abilene, Texas, United States

Mary Crowley Cancer Research Centers

Dallas, Texas, United States

Allison Cancer Center, Texas Oncology, P.A.

Midland, Texas, United States

Tyler Cancer Center, Texas Oncology

Tyler, Texas, United States

Seattle Cancer Care Alliance/Fred Hutchinson Cancer Res Ctr/Univ. of Washington Med Ctr

Seattle, Washington, United States

Davis Memorial Cancer Care Center

Elkins, West Virginia, United States

Marshfield Clinic Weston Center

Weston, Wisconsin, United States

University of Alberta Cross Cancer Institute

Edmonton, Alberta, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Orszagos Koranyi TBC es Pulmonologiai Intezet

Budapest, , Hungary

Semmelweis Egyetem Pulmonológiai Klinika

Budapest, , Hungary

Országos Korányi TBC és Pulmonológiai Intézet

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 Tüdőgyógyintézet

Törökbálint, , Hungary

Gujarat Cancer Hospital and Research Institute

Ahmedabad, , India

SEAROC Cancer Center, S.K.

Jaipur, , India

Tata Memorial Hospital

Mumbai, , India

Noble Hospital

Pune, , India

Ziekenhuis Groep Twente - locatie Twenteborg Ziekenhuis

Almelo, , Netherlands

Academisch Medisch Centrum

Amsterdam, , Netherlands

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

Universitair Medisch Centrum Maastricht

Maastricht, , Netherlands

Akademickie Centrum Kliniczne Szpital Akademii Medycznej w Gdansku

Gdansk, , Poland

Wielkopolskie Centrum Pulmunologii i Torakochirurgii

Poznan, , Poland

Centrum Onkologii - Instytut im.Marii Sklodowskiej-Curie

Warsaw, , Poland

Dolnoslaskie Centrum Chorob Pluc

Wroclaw, , Poland

Klinicko-bolnicki centar Bezanijska kosa

Belgrade, , Serbia

Institute for pulmonary disease Sremska Kamenica

Kamenitz, , Serbia

Klinicki Centar Nis

Niš, , Serbia

The Beatson West of Scotland Cancer Centre

Glasgow, Glasgow, United Kingdom

Clatterbridge Centre for Oncology

Bebington, Wirral, , United Kingdom

Ninewells Hospital and Medical School

Dundee, , United Kingdom

Guy's Hospital

London, , United Kingdom

Countries

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

References

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.

Reference Type: BACKGROUND

PMID: 16826191 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19287371 (View on PubMed)

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.

Reference Type: RESULT

PMID: 16966690 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26283035 (View on PubMed)

Related Links

http://www.novarx.com

Main sponsor website

Other Identifiers

BB-IND 8868

Identifier Type: -

Identifier Source: secondary_id

NR001-03

Identifier Type: -

Identifier Source: org_study_id

NCT00641966

Identifier Type: -

Identifier Source: nct_alias