Vaccine Therapy in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer - Full Text View

Sponsors and Collaborators:	Jonsson Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00601094

Purpose

RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer.

Condition	Intervention	Phase
Lung Cancer	Biological: autologous dendritic cell-adenovirus CCL21 vaccine Genetic: polymerase chain reaction Genetic: reverse transcriptase-polymerase chain reaction Other: flow cytometry Other: immunoenzyme technique Other: immunohistochemistry staining method	Phase I

MedlinePlus related topics: Cancer Lung Cancer

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
Official Title:	A Phase I Trial of CCL21 Gene Modified Dendritic Cells In Non-Small Cell Lung Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety [ Designated as safety issue: Yes ]
Maximum tolerated dose [ Designated as safety issue: Yes ]
Toxicity as measured by NCI Common Toxicity Criteria [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Disease status at days 28 and 56 [ Designated as safety issue: No ]
Immune response assessment by antigen-specific IFNγ ELISPOT assays on days 0, 28, and 56 [ Designated as safety issue: No ]

Estimated Enrollment:	21
Study Start Date:	February 2009
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To determine the safety, toxicity, and maximum tolerated dose (MTD) of autologous dendritic cell-adenovirus CCL21 vaccine administered as an intratumoral injection in treating patients with stage IIIB, IV, or recurrent non-small cell lung cancer.

Secondary

To determine the biologic and clinical responses to therapy.
To determine treatment-related toxicity using the NCI Common Toxicity Criteria.
To identify the MTD.
To monitor patients for evidence of autologous dendritic cell-adenovirus CCL21 vaccine-induced cytokines and antigen-specific immune responses.
To detect immune responses to tumor-associated antigens and vector.
To assess patients for objective signs of tumor regression (RECIST Criteria).

OUTLINE: This is a dose-escalation study of autologous dendritic cell-adenovirus CCL21 vaccine.

Patients undergo leukapheresis to obtain leukocytes for generation of autologous dendritic cells (DC). Adenovirus carrying the CCL21 gene is added to the dendritic cells to make the vaccine. Approximately 2 weeks after leukapheresis, patients receive an intratumoral injection of autologous dendritic cell-adenovirus CCL21 vaccine under CT-guidance or by bronchoscopy on days 0 and 7. Patients demonstrating a clinical response are eligible to receive a second round of gene transfer at their discretion and in consultation with the FDA.

Cohorts of 3 patients receive escalating doses of autologous dendritic cell-adenovirus CCL21 vaccine until the maximum tolerated dose (MTD) is determined. An additional 12 patients are treated at the MTD.

Patients undergo blood sample collection at baseline and then on days 0, 7, 14, 28, and 56 for safety and immunological studies. Blood samples are analyzed for mycoplasma by PCR; dendritic cell phenotype by flow cytometry; detection of adenovirus CCL21 by nested PCR; and adenoviral antibodies by ELISA. Patients also undergo tissue aspirate or biopsy on days 0 and 7 (during bronchoscopy or CT-guided procedure). Tissue samples are analyzed for immune-modulating cytokines (i.e., IFNγ, CXCL9, and CXCL10) by quantitative RT-PCR; detection of tumor infiltrating leukocytes by immunohistochemistry; CD83+ DC, CXCR3, CCR7, CCL21 and CD3+ T-cells, CD4, and CD8 by flow cytometry; determination of tumor expression of tumor-associated antigen by RT-PCR; and evaluation of immune modulation by ELISPOT assays.

After completion of study treatment, patients are followed periodically.

Eligibility

Ages Eligible for Study:	21 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Pathologically confirmed non-small cell lung cancer (NSCLC)
- Stage IIIB, IV, or recurrent disease
- Progressive disease despite one or more prior chemotherapy regimens as standard of care OR patient refuses standard chemotherapy
Measurable metastatic disease by RECIST guidelines
Patients with a major endobronchial lesion in the segmental, lobar, or mainstem bronchus with complete obstruction of the airway may be eligible for bronchoscopic injection provided there is no evidence of respiratory failure (defined as SaO_2 > 90% on room air, PCO_2 < 45 mm Hg, or FEV_1 > 1.0 L)
Patients with an endobronchial lesion in the segmental bronchus with variable stenosis (not completely obstructed) and not amenable to standard palliative airway treatments (i.e., laser and stenting) may be eligible for bronchoscopic injection if there is no evidence of respiratory failure (defined as SaO_2 > 90% on room air, PCO_2 < 45 mm Hg, or FEV_1 > 1.0 liters)
Patients with bullous disease may undergo CT-guided transthoracic injection provided the targeted tumor has an intended needle path without crossing bullae
No active CNS metastasis (i.e., progression of CNS disease during the past 30 days without intervention)

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
BUN ≤ 40 OR serum creatinine ≤ 2
Serum total bilirubin ≤ 1.5 OR serum transaminases ≤ 2.5 times upper limit of normal (ULN)
No evidence of coagulopathy, defined as PT and/or PTT ≤ 1.5 times ULN OR platelets ≥ 100,000/mm^3
No evidence of leukoplakia, defined as absolute neutrophil count ≥ 1,500/mm^3
No evidence of respiratory failure (defined as SaO_2 > 90% on room air, PCO_2 < 45 mm Hg, or FEV_1 > 1.0 L)
No NYHA class III-IV cardiac disease within the past year
No myocardial infarction within the past year
No comorbid disease or medical condition that would impair the ability of the patient to receive or comply with the study protocol
No acute viral, bacterial, or fungal infection that requires specific therapy
No HIV positivity
No hypersensitivity to any reagents used in the study
No signs or symptoms of acute adenoviral infection (i.e., conjunctivitis or documented adenoviral upper respiratory infection)
No prior or concurrent evidence of autoimmune disease
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

No prior organ allograft
More than 14 days since prior acute therapy for viral, bacterial, or fungal infections
More than 30 days since prior and no concurrent corticosteroids
More than 30 days since prior radiotherapy, chemotherapy, or noncytotoxic investigational agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00601094

Locations

United States, California
Jonsson Comprehensive Cancer Center at UCLA	Recruiting
Los Angeles, California, United States, 90095-1781
Contact: Clinical Trials Office - Jonsson Comprehensive Cancer Center a 888-798-0719

Sponsors and Collaborators

Jonsson Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Jay M. Lee, MD

Jonsson Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000579276, UCLA-NCI-7888
Study First Received:	January 10, 2008
Last Updated:	February 27, 2009
ClinicalTrials.gov Identifier:	NCT00601094 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent non-small cell lung cancer

Study placed in the following topic categories:

Thoracic Neoplasms
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Non-small Cell Lung Cancer

Carcinoma, Non-Small-Cell Lung
Recurrence
Neoplasms, Glandular and Epithelial
Carcinoma

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 May 06, 2009