Eligibility:
- Individuals at least 18 years of age who have primary small cell or non-small cell lung cancer, esophageal cancer, or pleural mesothelioma that can be removed by surgery.
- Only individuals whose tumor cells are able to produce a tumor cell line for vaccine development will be eligible for treatment.
Design:
- Participants will be screened with a physical examination and medical history, and will have tumor tissue collected during their surgery to determine whether the tumor cells can be used to produce a vaccine.
- Participants will take celecoxib twice daily for 7 days before having the first tumor cell vaccination. Participants will also have leukapheresis to collect blood cells for testing before the first vaccination.
- Participants will receive one vaccine (which may be given in two shots) monthly for 6 months, and will continue to take celecoxib twice daily. One month after the 6th vaccine shot, participants will have another leukapheresis and skin test. If these tests show that a participant is responding to the vaccine, additional vaccines will be given every 3 months for up to 2 years.
- Participants will have a physical exam and lab tests before each vaccination, blood samples and imaging studies every 3 months, and a skin test every 6 months.
- Participants will have regular followup visits with imaging studies and blood samples …
Intervention Details:
- Drug: Celecoxib
- 400 mg PO, BID, continuously, until 1 month after last vaccination
- Drug: ISCOMATRIX (TM) Adjuvant
- Adjuvant mixed with vaccine at 180 ISCO (TM) units/mL
- Biological: Autologous Tumor Cell Vaccine
- 1×10(7) – 1×10(8) cells emulsified in ISCOMATRIX(TM) adjuvant, SC, q 4 wk for 6 months.
Detailed Description:
Background:
- Cancer-testis (CT) antigens have emerged as attractive targets for cancer immunotherapy. Whereas lung and esophageal cancers, as well as malignant pleural mesotheliomas express a variety of CT antigens, primary or vaccine-induced immune responses to these antigens appear uncommon in patients with these malignancies, possibly due to low-level, heterogeneous antigen expression, and inadequate vaccination strategies.
- Because numerous CT antigens can be induced in tumor cells by DNA demethylating agents and HDAC inhibitors, it is conceivable that vaccination of cancer patients with autologous tumor cells exposed to chromatin remodeling agents will enhance anti-tumor immunity in these individuals.
- In order to examine this issue, patients with resectable primary neoplasms involving the lungs, esophagus, or pleura will be vaccinated with autologous tumor cells exposed exvivo to decitabine and radiation following completion of appropriate combined modality therapy. Vaccine will be administered in conjunction with ISCOMATRIX(Trademark) adjuvant and oral celecoxib.
Primary Objective:
- To assess the safety of an epigenetically modified autologous tumor cell vaccine in conjunction with celecoxib.
Eligibility:
- Patients with histologically or cytologically proven primary pulmonary carcinoma or sarcoma, esophageal cancer, or malignant pleural mesothelioma undergoing resection of their neoplasms.
- Patients must be 18 years or older with an ECOG performance status of 0 – 2, with adequate pulmonary and cardiac function and laboratory values within normal limits.
Design:
- Patients with operable lung and esophageal carcinoma/sarcoma, or malignant pleural mesothelioma will undergo resection of their malignancies at the NCI.
- Portions of the resected tumors will be transferred to the Thoracic Oncology Laboratory. Aliquots of tumor digests will be frozen in liquid nitrogen for future use, and some cells will be processed to establish a cancer cell line.
- Following recovery from surgery and appropriate adjuvant chemotherapy and/or radiation, patients will be vaccinated with epigenetically-modified autologous tumor cells periodically over 6 months in conjunction with oral celecoxib.
- Systemic toxicities and delayed type hypersensitivity responses to autologous tumor cells and serologic responses to a variety of CT antigens will be assessed before and after vaccination.
- Patients will be followed with routine staging scans until disease recurrence.
- As the exact set of comparisons and analyses to be performed will be determined following completion of the trial, and will be based on limited numbers of patients, the analyses will be considered exploratory and hypothesis generating rather than definitive.
- Approximately 120 patients will be accrued to this trial in order to obtain up to 30 evaluable patients.
