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

Phase 3
Completed
Conditions
Carcinoma Non-small Cell Lung Cancer Stage IIIB
Carcinoma Non-small Cell Lung Cancer Stage IV
Lung Neoplasm
Carcinoma Non-small Cell Lung Cancer Stage IIIA
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
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
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
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
Evaluate the rate of CNS metastases development in subjects treated with Lucanix™ as compared to the Best Supportive Care control group.7 years

Trial Locations

Locations (74)

Southern Cancer Center

🇺🇸

Mobile, Alabama, United States

Alaska Regional Hospital

🇺🇸

Anchorage, Alaska, United States

Mayo Clinic Cancer Center

🇺🇸

Rochester, Minnesota, 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

Scroll for more (64 remaining)
Southern Cancer Center
🇺🇸Mobile, Alabama, United States

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