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Phase III Lucanix™ Vaccine Therapy in Advanced Non-small Cell Lung Cancer (NSCLC) Following Front-line Chemotherapy (STOP)
This study is currently recruiting participants.
Verified by NovaRx Corporation, January 2010
First Received: May 8, 2008   Last Updated: January 27, 2010   History of Changes
Sponsor: NovaRx Corporation
Information provided by: NovaRx Corporation
ClinicalTrials.gov Identifier: NCT00676507
  Purpose

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.


Condition Intervention Phase
Lung Neoplasm
Carcinoma, Non-Small-Cell Lung: Stage IIIA (T3,N2 Only)
Carcinoma, Non-Small-Cell Lung: Stage IIIB
Carcinoma, Non-Small-Cell Lung: Stage IV
 Biological: Lucanix™
Other: Placebo Comparator
 Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
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

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics
MedlinePlus related topics: Cancer Lung Cancer
U.S. FDA Resources

Further study details as provided by NovaRx Corporation:

Primary Outcome Measures:
  • Compare the overall survival of subjects with stage III or IV non-small cell lung cancer treated with belagenpumatucel-L (Lucanix™) vs placebo. [ Time Frame: 7 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate the progression free survival (PFS) of subjects treated with Lucanix™ compared to treatment within the Best Support Care control group. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Evaluate the time-to-progression of subjects treated with Lucanix™ compared to treatment within the Best Supportive Care control group. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Evaluate the best overall tumor response in subjects treated with Lucanix™ compared to treatment in the Best Supportive Care control group. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Evaluate the response duration in subjects treated with Lucanix™ compared to the Best Supportive Care control group. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Evaluate the rate of CNS metastases development in subjects treated with Lucanix™ as compared to the Best Supportive Care control group. [ Time Frame: 7 years ] [ Designated as safety issue: No ]
  • Adverse events of subjects treated with Lucanix™ will be compared to subjects in the Best Supportive Care control group. [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 700
Study Start Date: July 2008
Estimated Study Completion Date: October 2011
Estimated Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Treatment: Experimental
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.
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.
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.
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.

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00676507

  Hide Study Locations
Locations
United States, Arizona
Mayo Clinic Cancer Center Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Tracy Keller, RN BSN     480-301-6767     keller.tracy@mayo.edu    
Principal Investigator: Helen Ross, MD            
United States, California
University of California, San Diego Recruiting
La Jolla, California, United States, 92093
Contact: Kelly Souder     858-822-7952     knsouder@ucsd.edu    
Principal Investigator: Lyudmila Bazhenova, MD            
United States, Florida
Pasco Hernando Oncology Associates, P.A. Recruiting
Brooksville, Florida, United States, 34613
Contact: Kim Graves, RN     352-596-1401 ext 218     kgraves@phoa4.com    
Principal Investigator: Raju Rao, MD            
United States, Georgia
Atlanta Cancer Care Recruiting
Roswell, Georgia, United States, 30076
Contact: Julie Carney, RN     678-287-1241     jcarney@atlantacancercare.com    
Principal Investigator: Ronald Steis, MD            
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Debbie Pach     312-563-3347     deborah_b_pach@rush.edu    
Principal Investigator: Philip D Bonomi, MD            
Warren Billhartz Cancer Center Recruiting
Maryville, Illinois, United States, 62062
Contact: Wendy McIntyre     618-391-5900     mcintyrew@andersonhospital.org    
Principal Investigator: John Visconti, MD            
United States, Iowa
Iowa Blood and Cancer Center Recruiting
Cedar Rapids, Iowa, United States, 52402
Contact: Carlene Etscheidt, RN     319-369-7091     cetscheidt@ibacc.org    
Principal Investigator: David W. Zenk, MD            
United States, Louisiana
Hematology Oncology Life Center Recruiting
Alexandria, Louisiana, United States, 71301
Contact: Carla Ouber, RN     318-442-2232 ext 3068     research@holcmed.com    
Principal Investigator: Howard Wold, MD            
United States, Maryland
National Cancer Institute Center for Cancer Research, Medical Oncology Branch Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Corrine M Keen, RN, MS, OCN     301-496-3778     ckeen@mail.nih.gov    
Principal Investigator: Giuseppe Giaccone, MD, PhD            
United States, Minnesota
Mayo Clinic Cancer Center Recruiting
Rochester, Minnesota, United States, 55905
Contact: Angie Meilander     507-284-2030     meilander.angela@mayo.edu    
Principal Investigator: Julian R. Molina, MD            
University of Minnesota Medical Center Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Debra Herzan, RN, BSN, OCN     612-626-4495     herza001@umn.edu    
Principal Investigator: Arkadiusz Dudek, MD, PhD            
United States, North Carolina
Carolina BioOncology Institute Recruiting
Huntersville, North Carolina, United States, 28078
Contact: Jahleen Byers     704-947-6599     jbyers@carolinabiooncology.org    
Principal Investigator: John Powderly, II, MD            
Cancer Care of WNC Recruiting
Asheville, North Carolina, United States, 28801
Contact: Candace Cox     828-253-4262     candace@cancercareofwnc.com    
Principal Investigator: Christopher Chay, MD            
United States, Ohio
Gabrail Cancer Center Research LLC Recruiting
Canton, Ohio, United States, 44718
Contact: Carrie Smith, RN     330-492-3345     csmith@gabrailcancercenter.com    
Principal Investigator: Neshat Gabrail, MD            
United States, Oklahoma
Optim Oncology Recruiting
Midwest City, Oklahoma, United States, 73110
Contact: Jude Knapp     405-737-8455     jknapp@optimoncology.com    
Principal Investigator: Stephen A Hamilton, MD            
United States, South Carolina
Cancer Center of the Carolinas Recruiting
Greenville, South Carolina, United States, 29605
Contact: Lisa Johnson, RN, BSN     864-679-3966     lisa.johnson@usoncology.com    
Principal Investigator: Joe Stephenson, MD            
Charleston Hematology Oncology Associates, PA Recruiting
Charleston, South Carolina, United States, 29403
Contact: Deborah McNeal, RN, OCN     843-266-2540     d.mcneal@choasc.com    
Principal Investigator: David M Ellison, MD            
Coastal Cancer Center Recruiting
Myrtle Beach, South Carolina, United States, 29572
Contact: Carla Gatti     843-429-5042     clinicaltrials@coastalcancercenter.com    
Principal Investigator: Lawrence B. Holt, MD FACP            
United States, Texas
Mary Crowley Cancer Research Centers Recruiting
Dallas, Texas, United States, 75246
Contact: Kay Easterwood-Sanchez     214-658-1943     keasterwoodsanchez@marycrowley.org    
Principal Investigator: John J. Nemunaitis, MD            
Allison Cancer Center, Texas Oncology, P.A. Recruiting
Midland, Texas, United States, 79701
Contact: Sarah Turner, BS     432-686-5715     sara.turner@usoncology.com    
Principal Investigator: David Watkins, MD            
Tyler Cancer Center, Texas Oncology Recruiting
Tyler, Texas, United States, 75702
Contact: Linda Dunklin, RN, OCN     903-579-9867     linda.dunklin@usoncology.com    
Principal Investigator: Donald A Richards, MD            
Texas Cancer Center Abilene, Texas Oncology P.A. Recruiting
Abilene, Texas, United States, 79606
Contact: Tammie Coffman, RN     325-692-0188     tammie.coffman@usoncology.com    
Principal Investigator: Anton Melnyk, MD            
United States, Washington
Seattle Cancer Care Alliance/Fred Hutchinson Cancer Res Ctr/Univ. of Washington Med Ctr Recruiting
Seattle, Washington, United States, 98109
Contact: Kari Stricker     206-288-7481     kstricke@uw.edu    
Principal Investigator: Keith D. Eaton, MD, PhD            
United States, Wisconsin
Marshfield Clinic Weston Center Recruiting
Weston, Wisconsin, United States, 54476
Contact: Cyndi Ehrike, RN     715-393-1496     ehrike.cynthia@marshfieldclinic.org    
Principal Investigator: Adedayo Onitilo, MD            
Canada, Alberta
University of Alberta Cross Cancer Institute Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Romeo Felix, RN     780-577-8048     romeofel@cancerboard.ab.ca    
Principal Investigator: Quincy S-C Chu, MD            
Canada, Ontario
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Dianne Zawisza     416-946-2913     dianne.zawisza@uhn.on.ca    
Principal Investigator: Natasha Leighl, MD            
Hungary
Pest Megyei Tüdőgyógyintézet Recruiting
Törökbálint, Hungary, 2045
Contact: Kovács Katalin     +36 23 511 562     orvosigazgato@tbti.t-online.hu    
Principal Investigator: Edina Tolnay, MD            
Országos Korányi TBC és Pulmonológiai Intézet Recruiting
Budapest, Hungary, 1529
Contact: Barna Tímea     +36 1 391 3277     timeabarna@freemail.hu    
Principal Investigator: Erzsébet Juhász, MD            
Csongrád Megyei Önkormányzat Mellkasi Betegségek Szakkórháza Recruiting
Deszk, Hungary, 6772
Contact: Wentné Rádin Ruzsica     +36 62 571 512     titkarsag@deszkikorhaz.hu    
Principal Investigator: Beatrix Bálint, MD            
Semmelweis Egyetem Pulmonológiai Klinika Recruiting
Budapest, Hungary, 1125
Contact: Gabriella Zahorecz     +36-1-355-9733     zahoreczg@freemail.hu    
Principal Investigator: György Losonczy, MD            
Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András Oktató Kórháza Recruiting
Nyíregyháza, Hungary, 4412
Contact: Ildiko Madai     +36-20-316-9483     pulmo1@josa.hu    
Principal Investigator: Ilona Vinkler, MD            
Fejér Megyei Szent György Kórház Recruiting
Székesfehérvár, Hungary, 8000
Contact: Gábor Grmela     +36-20-823-6496     ggrmela@mail.fmkorhaz.hu    
Principal Investigator: Zsolt Pápai-Székely, MD            
India
SEAROC Cancer Center, S.K. Recruiting
Jaipur, India, 302013
Contact: Anish Maru, MD     + 91 9829060128     anishmaru@yahoo.com    
Principal Investigator: Ansih Maru, MD            
Apollo Hospitals Recruiting
Hyderabad, India, 500033
Contact: Srinivas Chakravarthy Gummaraju, MD     + 91 9989299091     hydaherf@gmail.com    
Principal Investigator: Srinivas Chakravarthy Gummaraju, MD            
Regional Cancer Centre Not yet recruiting
Trivandrum, India, 695011
Contact: Sivanandan Choondal Devan, MD     + 91 9447882149     sivanandancd@hotmail.com    
Principal Investigator: Sivanandan Choondal Devan, MD            
Tata Memorial Hospital Recruiting
Mumbai, India, 400012
Contact: Prabhash Kumar, MD     + 91 9224182898     kp_prabhash@rediffmail.com    
Principal Investigator: Prabhash Kumar, MD            
Gujarat Cancer Hospital and Research Institute Recruiting
Ahmedabad, India, 380016
Contact: Harsha Panchal, MD     + 91 9825940769     drharshapanchal@hotmail.com    
Principal Investigator: Harsha Panchal, MD            
Serbia
Klinicko-bolnicki centar Bezanijska kosa Recruiting
Belgrade, Serbia, 11000
Contact: Danka Kavurin     +381 64 2631263        
Principal Investigator: Vladimir Kovcin, MD            
Klinicki Centar Nis Recruiting
Nis, Serbia, 18000
Contact: Marina Cekic, MD     +381 64 1118223     Marina.cekic@gmail.com    
Principal Investigator: Milan Rancic, MD            
Institute for pulmonary disease Sremska Kamenica Recruiting
Sremska Kamenica, Serbia, 21204
Contact: Daliborka Bursac, MD     +381 64 2839713     Jelena_bb@neobee.net    
Principal Investigator: Nevena Secen, MD            
United Kingdom
Clatterbridge Centre for Oncology Recruiting
Bebington, Wirral, United Kingdom, CH63 4JY
Contact: Joanne Upton     +44-151-334-1155 ext 5731     joanne.upton@ccotrust.nhs.uk    
Principal Investigator: Ernest Marshall, MD            
Ninewells Hospital and Medical School Recruiting
Dundee, United Kingdom, DD1 9SY
Contact: Debbie Forbes     +44-1382-660-111     debbieforbes@nhs.net    
Principal Investigator: Elaine Rankin, MD            
Guy's Hospital Recruiting
London, United Kingdom, SE1 9RT
Contact: Sharon Delena     +44-207-188-2006 ext 87752     sharon.delena@gstt.nhs.uk    
Principal Investigator: Rohit Lal, MD            
Glasgow Royal Infirmary Recruiting
Glasgow, United Kingdom, G12 0YN
Contact: Calum Innes     +44-141-301-7224     calum.ines@northglasgow.scot.nhs.uk    
Principal Investigator: David Dunlop, MD            
Sponsors and Collaborators
NovaRx Corporation
  More Information

Additional Information:
Main sponsor website  This link exits the ClinicalTrials.gov site
Clinical trial information  This link exits the ClinicalTrials.gov site

Publications:
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. Epub 2006 Sep 11.
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.

Responsible Party: NovaRx Corporation ( Habib Fakhrai, Ph.D., President & Executive Vice Chairman )
Study ID Numbers: NR001-03, BB-IND 8868
Study First Received: May 8, 2008
Last Updated: January 27, 2010
ClinicalTrials.gov Identifier: NCT00676507     History of Changes
Health Authority: United States: Food and Drug Administration;   Italy: National Institute of Health;   United States: Institutional Review Board;   Canada: Health Canada;   United Kingdom: Medicines and Healthcare Products Regulatory Agency;   Germany: Paul-Ehrlich-Institut;   Poland: Ministry of Health;   Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products;   Hungary: National Institute of Pharmacy;   Italy: Ministry of Health;   Serbia and Montenegro: Agency for Drugs and Medicinal Devices;   India: Central Drugs Standard Control Organization

Keywords provided by NovaRx Corporation:
Gene therapy
Flow cytometry
Immunoenzyme technique
 Laboratory biomarker analysis
Quality-of-life-assessment
Tumor cell-derivative vaccine therapy

Additional relevant MeSH terms:
Thoracic Neoplasms
Respiratory Tract Neoplasms
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Respiratory Tract Diseases
 Lung Neoplasms
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Carcinoma

ClinicalTrials.gov processed this record on February 04, 2010



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