Vaccine Therapy, Tretinoin, and Cyclophosphamide in Treating Patients With Metastatic 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.
Biological: Vaccine Treatment
Drug: All-trans retinoic acid (ATRA)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Combination Immunotherapy for Lung Cancer|
- Number of Evaluable Participants With Tumor Response [ Time Frame: 3 years ] [ Designated as safety issue: No ]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.
- Median Time to Progression (TTP) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]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.
|Study Start Date:||October 2006|
|Study Completion Date:||June 2012|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
Experimental: Combination Immunotherapy
Vaccine + Cytoxan + ATRA as outlined in Detailed Description
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 VaccinesDrug: Cyclophosphamide
Cyclophosphamide (300 mg/m^2 IV) was administered before 1st and 4th vaccines to deplete regulatory T-cells.
Other Name: cytoxanDrug: 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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00601796
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612-9497|
|Principal Investigator:||Alberto Chiappori, MD||H. Lee Moffitt Cancer Center and Research Institute|