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Vaccine Therapy, Tretinoin, and Cyclophosphamide in Treating Patients With Metastatic Lung Cancer

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ClinicalTrials.gov Identifier: NCT00601796
Recruitment Status : Completed
First Posted : January 28, 2008
Results First Posted : May 15, 2013
Last Update Posted : May 24, 2013
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Institutes of Health (NIH)
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

January 19, 2008
January 28, 2008
February 27, 2013
May 15, 2013
May 24, 2013
October 2006
June 2012   (Final data collection date for primary outcome measure)
Number of Evaluable Participants With Tumor Response [ Time Frame: 3 years ]
Number of participants with evaluable peripheral blood mononuclear cells (PBMCs) who demonstrated sustained tumor peptide-specific T-cell activation after vaccination. Peripheral blood mononuclear cells (PBMCs) were collected at baseline and after each vaccination. T-cell activation profiles were analyzed by ELISpot assay and tested by generalized Wilcoxon for correlation to survival.
Tumor response
Complete list of historical versions of study NCT00601796 on ClinicalTrials.gov Archive Site
  • Median Time to Progression (TTP) [ Time Frame: 3 years ]
    Analysis of Time to Progression and Survival Endpoints. All patients will be considered in the analysis of progression free survival time (time from start of treatment to progression or death) and survival time (time from initiation of treatment to death). Progression is defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Follow-up for this analysis will continue for all patients for their lifetimes. Time to progression and survival probabilities over time will be calculated by the method of Kaplan-Meier.
  • Median Overall Survival (OS) [ Time Frame: 3 years ]
    Analysis of Time to Progression and Survival Endpoints. All patients will be considered in the analysis of progression free survival time (time from start of treatment to progression or death) and survival time (time from initiation of treatment to death). Follow-up for this analysis will continue for all patients for their lifetimes. Time to progression and survival probabilities over time will be calculated by the method of Kaplan-Meier.
  • Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: 3 years ]
    Toxicity will be assessed using the NCI Common Terminology Criteria for Adverse Criteria (CTAE-3),Version 3.0 (www.ctep.cancer.gov). Particular attention will assess the presence of symptomatic lymphadenopathy or any local skin / soft tissue reaction at the vaccine site. Blood tests for ANA and rheumatoid factor will be performed on any patient who develops evidence of autoimmune phenomena.
  • Time to progression
  • Survival
Not Provided
Not Provided
 
Vaccine Therapy, Tretinoin, and Cyclophosphamide in Treating Patients With Metastatic Lung Cancer
Combination Immunotherapy for Lung Cancer
The purpose of this study is to find out what effects (good and/or bad) a tumor vaccine used in combination with two drugs (ATRA and cytoxan) have on the patient and their cancer. We also want to find out if the vaccine and the drugs can boost the patient's immune system and how their immune system reacts, both before and after the vaccine treatment.
This protocol describes a phase II study involving patients with stage IV adenocarcinoma of the lung. Treatment will consist of Cyclophosphamide (300 mg/m²) to be given IV on day 1 and day 57. On day 4 immunization with intradermal vaccine injections at 4 separate sites (bilateral upper arms and bilateral upper thighs will be repeated every 14 days times 2 followed by every 28 days times 3 (day 4, 18, 32, 60, 88, and 116). Decavac (tetanus shot) 0.5 cc intramuscular (IM) will be given after the first vaccine. ATRA (150 mg/m2/day) oral three times daily (TID) dosing administered after the first and fourth vaccines (day 5-7 & day 61-63). Those patients achieving stable disease (SD), partial response (PR), or complete response (CR) at restaging after the initial 6 vaccines will receive additional vaccines every 3 months until disease progression. The vaccine will consist of GM.CD40L bystander cells admixed with an equivalent number of the 2 allogeneic tumor cell lines. There will be a +/- 7 day window for all study related exams, tests, and procedures.
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Lung Cancer
  • Biological: Vaccine Treatment
    We created a vaccine in which irradiated allogeneic lung adenocarcinoma cells are combined with a bystander K562 cell line transfected with hCD40L and hGM-CSF. By recruiting and activating dendritic cells, we hypothesized the vaccine would induce tumor regression in metastatic lung adenocarcinoma. Intradermal vaccine was given every 14 days x3, followed by monthly x3.
    Other Name: Allogeneic Tumor Cell-Based Vaccines
  • Drug: Cyclophosphamide
    Cyclophosphamide (300 mg/m^2 IV) was administered before 1st and 4th vaccines to deplete regulatory T-cells.
    Other Name: cytoxan
  • Drug: All-trans retinoic acid (ATRA)
    All-trans retinoic acid was given (150/mg/m^2/day) after 1st and 4th vaccines to enhance dendritic differentiation.
    Other Names:
    • Vesanoid®
    • tretinoin
    • all trans retinoic acid
    • ATRA
Experimental: Combination Immunotherapy
Vaccine + Cytoxan + ATRA as outlined in Detailed Description
Interventions:
  • Biological: Vaccine Treatment
  • Drug: Cyclophosphamide
  • Drug: All-trans retinoic acid (ATRA)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
48
June 2012
June 2012   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed metastatic adenocarcinoma of the lung
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1
  • No radiation therapy within 2 weeks of first vaccine administration
  • No chemotherapy within 4 weeks of first vaccine administration
  • No steroid therapy within 4 weeks of first vaccine administration
  • Patient's written informed consent
  • Adequate organ function (measured within a week of beginning treatment)
  • Patients will be tested for human leukocyte antigen A0201 (HLA-A0201) as determined by flow cytometry followed by molecular analysis of a peripheral blood specimen, however this result will not be an inclusion criterion.
  • Measurable metastatic tumor as defined by standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Lesions must be accurately measured in at least one dimension with the longest diameter greater than or equal 20mm. With spiral computer tomography (CT) scan, lesion must be greater than or equal to 10 mm at least one dimension.
  • Patient's must have received, and completed first line chemotherapy.

Exclusion Criteria:

  • Symptomatic brain metastasis
  • Any acute medical problems requiring active intervention
  • Current corticosteroid (other than replacement doses in patients who are hypoadrenal) or other immunosuppressive therapy
  • Any other pre-existing immunodeficiency condition (including known HIV infection)
  • Pregnant or lactating women -- Patients in reproductive age must agree to use contraceptive methods for the duration of the study (*A pregnancy test will be obtained before treatment).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 2, 3 or 4
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00601796
MCC-14744
P30CA076292 ( U.S. NIH Grant/Contract )
NIH-OBA-0608-801 ( Other Identifier: National Institute of Health )
Yes
Not Provided
Not Provided
H. Lee Moffitt Cancer Center and Research Institute
H. Lee Moffitt Cancer Center and Research Institute
  • National Cancer Institute (NCI)
  • National Institutes of Health (NIH)
Principal Investigator: Alberto Chiappori, MD H. Lee Moffitt Cancer Center and Research Institute
H. Lee Moffitt Cancer Center and Research Institute
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP