Phase III Lucanix™ Vaccine Therapy in Advanced Non-Small Cell Lung Cancer (NSCLC) Following Front-Line Chemotherapy - Full Text View

Sponsored by:	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

MedlinePlus related topics: Cancer Lung Cancer

U.S. FDA Resources

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

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 one month nor more than four months must have elapsed since the completion of the last chemotherapy cycle and registration into the study.
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 ≥ 3.5 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.
Objective evidence of brain metastases.
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

Locations

United States, California
University of California, San Diego	Recruiting
La Jolla, California, United States, 92093
Contact: Peter Vu 858-822-7952 pvu@ucsd.edu
Principal Investigator: Lyudmila Bazhenova, MD
United States, Illinois
Rush University Medical Center	Not yet 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	Not yet 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, Maryland
National Cancer Institute Center for Cancer Research, Medical Oncology Branch	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Arlene Berman 301-435-5609 arleneb@mail.nih.gov
Principal Investigator: Giuseppe Giaccone, MD, PhD
United States, Minnesota
Mayo Clinic Cancer Center	Not yet 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, Oklahoma
Optim Oncology	Recruiting
Midwest City, Oklahoma, United States, 73110
Contact: Rebecca Lowery, RN, BSN 405-737-8455 blowery@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
United States, Texas
Mary Crowley Cancer Research Centers	Recruiting
Dallas, Texas, United States, 75246
Contact: J.R. Doan, CCRA 214-658-1943 jdoan@marycrowley.org
Principal Investigator: John J. Nemunaitis, 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 206-667-5650 kstricke@fhcrc.org
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	Not yet 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	Not yet 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	Not yet recruiting
Deszk, Hungary, 6772
Contact: Wentné Rádin Ruzsica +36 62 571 512 titkarsag@deszkikorhaz.hu
Principal Investigator: Beatrix Bálint, 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

Sponsors and Collaborators

NovaRx Corporation

More Information

Main sponsor website This link exits the ClinicalTrials.gov site

Clinical trial information This link exits the ClinicalTrials.gov site

Publications of Results:

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.

Other Publications:

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:	December 23, 2008
ClinicalTrials.gov Identifier:	NCT00676507
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

Study placed in the following topic categories:

Thoracic Neoplasms
Non-small cell lung cancer
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases

Quality of Life
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Respiratory Tract Neoplasms
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on January 14, 2009