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

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

Show 72 Study Locations

Sponsors and Collaborators

NovaRx Corporation

More Information

Additional Information:

Main sponsor website 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 )
ClinicalTrials.gov Identifier:	NCT00676507 History of Changes
Obsolete Identifiers:	NCT00641966
Other Study ID Numbers:	NR001-03, BB-IND 8868
Study First Received:	May 8, 2008
Last Updated:	August 6, 2010
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:

Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 01, 2010