Phase III Lucanix™ Vaccine Therapy in Advanced Non-small Cell Lung Cancer (NSCLC) Following Front-line Chemotherapy
- Conditions
- Carcinoma Non-small Cell Lung Cancer Stage IIIBCarcinoma Non-small Cell Lung Cancer Stage IVLung NeoplasmCarcinoma Non-small Cell Lung Cancer Stage IIIA
- Interventions
- Other: Placebo ComparatorBiological: Lucanix™
- Registration Number
- NCT00676507
- Lead Sponsor
- NovaRx Corporation
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 532
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control Arm Placebo Comparator 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. Treatment Lucanix™ 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.
- Primary Outcome Measures
Name Time Method 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
- Secondary Outcome Measures
Name Time Method Evaluate the time-to-progression of subjects treated with Lucanix™ compared to treatment within the Best Supportive Care control group. 3 years Evaluate the best overall tumor response in subjects treated with Lucanix™ compared to treatment in the Best Supportive Care control group. 3 years Evaluate the response duration in subjects treated with Lucanix™ compared to the Best Supportive Care control group. 3 years Evaluate the progression free survival (PFS) of subjects treated with Lucanix™ compared to treatment within the Best Support Care control group. 3 years Evaluate the rate of CNS metastases development in subjects treated with Lucanix™ as compared to the Best Supportive Care control group. 7 years Adverse events of subjects treated with Lucanix™ will be compared to subjects in the Best Supportive Care control group. 7 years 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
Trial Locations
- Locations (74)
Centrum Onkologii - Instytut im.Marii Sklodowskiej-Curie
🇵🇱Warsaw, Poland
Klinicko-bolnicki centar Bezanijska kosa
🇷🇸Belgrade, Serbia
Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
Richmond University Medical Center
🇺🇸Staten Island, New York, United States
Cancer Care of WNC
🇺🇸Asheville, North Carolina, United States
Southern Cancer Center
🇺🇸Mobile, Alabama, United States
Alaska Regional Hospital
🇺🇸Anchorage, Alaska, United States
Clopton Clinic Hematology/Oncology
🇺🇸Jonesboro, Arkansas, United States
University of California, San Diego
🇺🇸La Jolla, California, United States
Cancer Care Associates
🇺🇸Redondo, California, United States
Sansum Clinic
🇺🇸Santa Barbara, California, United States
UCLA Pasadena Oncology
🇺🇸Pasadena, California, United States
Santa Barbara Hematology Oncology Medical Group, Inc.
🇺🇸Santa Barbara, California, United States
UCLA Cancer Center
🇺🇸Westlake Village, California, United States
Central Coast Medical Oncology Corporation
🇺🇸Santa Maria, California, United States
UCLA Cancer Center-Valencia
🇺🇸Valencia, California, United States
Pasco Hernando Oncology Associates, P.A.
🇺🇸Brooksville, Florida, United States
Medical Specialist of Palm Beaches
🇺🇸Lake Worth, Florida, United States
Space Coast Medical Center
🇺🇸Titusville, Florida, United States
Ocala Oncology
🇺🇸Ocala, 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
Hematology Oncology Life Center
🇺🇸Alexandria, Louisiana, United States
Iowa Blood and Cancer Center
🇺🇸Cedar Rapids, Iowa, United States
University of Tennessee Cancer Institute
🇺🇸Memphis, Tennessee, United States
Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Gabrail Cancer Center Research LLC
🇺🇸Canton, Ohio, United States
Allergy Partners of West North Carolina
🇺🇸Asheville, North Carolina, United States
Eastchester Center for Cancer Care
🇺🇸Bronx, New York, United States
Texas Cancer Center Abilene, Texas Oncology P.A.
🇺🇸Abilene, Texas, United States
Optim Oncology
🇺🇸Midwest City, Oklahoma, United States
Mary Crowley Cancer Research Centers
🇺🇸Dallas, Texas, United States
Seattle Cancer Care Alliance/Fred Hutchinson Cancer Res Ctr/Univ. of Washington Med Ctr
🇺🇸Seattle, Washington, United States
Allison Cancer Center, Texas Oncology, P.A.
🇺🇸Midland, Texas, United States
Marshfield Clinic Weston Center
🇺🇸Weston, Wisconsin, United States
Davis Memorial Cancer Care Center
🇺🇸Elkins, West Virginia, United States
Tyler Cancer Center, Texas Oncology
🇺🇸Tyler, Texas, United States
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
University of Alberta Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Orszagos Koranyi TBC es Pulmonologiai Intezet
🇭🇺Budapest, Hungary
Semmelweis Egyetem Pulmonológiai Klinika
🇭🇺Budapest, Hungary
Csongrád Megyei Önkormányzat Mellkasi Betegségek Szakkórháza
🇭🇺Deszk, Hungary
Fejér Megyei Szent György Kórház
🇭🇺Székesfehérvár, Hungary
Országos Korányi TBC és Pulmonológiai Intézet
🇭🇺Budapest, Hungary
Pest Megyei Tüdőgyógyintézet
🇭🇺Törökbálint, Hungary
Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András Oktató Kórháza
🇭🇺Nyíregyháza, Hungary
Gujarat Cancer Hospital and Research Institute
🇮🇳Ahmedabad, India
SEAROC Cancer Center, S.K.
🇮🇳Jaipur, India
Antoni van Leeuwenhoek Ziekenhuis
🇳🇱Amsterdam, Netherlands
Tata Memorial Hospital
🇮🇳Mumbai, India
Academisch Medisch Centrum
🇳🇱Amsterdam, Netherlands
Ziekenhuis Groep Twente - locatie Twenteborg Ziekenhuis
🇳🇱Almelo, Netherlands
Universitair Medisch Centrum Maastricht
🇳🇱Maastricht, Netherlands
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
Dolnoslaskie Centrum Chorob Pluc
🇵🇱Wroclaw, Poland
Klinicki Centar Nis
🇷🇸Nis, Serbia
Institute for pulmonary disease Sremska Kamenica
🇷🇸Sremska Kamenica, Serbia
The Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Clatterbridge Centre for Oncology
🇬🇧Bebington, Wirral, United Kingdom
Ninewells Hospital and Medical School
🇬🇧Dundee, United Kingdom
Noble Hospital
🇮🇳Pune, India
University of Minnesota Medical Center
🇺🇸Minneapolis, Minnesota, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Innovative Research Center of California
🇺🇸San Diego, California, United States
University of Colorado Health Science Center
🇺🇸Aurora, Colorado, United States
James Graham Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
National Cancer Institute Center for Cancer Research, Medical Oncology Branch
🇺🇸Bethesda, Maryland, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Cancer Center of the Carolinas
🇺🇸Greenville, South Carolina, United States
Guy's Hospital
🇬🇧London, United Kingdom