Autologous Tumor Cell Vaccs and ISCOMATRIX(TM) Adjuvant With Metronomic Oral Cyclophosphamide and Celecoxib in Pts Undergoing Resection of Sarcomas, Melanomas, Germ Cell Tumors, or Epithelial Malignancies Metastatic to Lungs, Pleura or Mediastinum
Cancer-testis (CT) antigens (CTAs) have emerged as attractive targets for cancer
immunotherapy. Whereas cancers of various histologies exhibit CTA expression, 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
undergoing complete resection of sarcomas, melanomas, germ cell tumors and epithelial
malignancies metastatic to the lungs, pleura or mediastinum will be vaccinated with
autologous tumor cells exposed ex-vivo to decitabine and radiation following completion of
appropriate combined modality therapy. Vaccines will be administered in conjunction with
ISCOMATRIX(Trademark) adjuvant as well as metronomic oral cyclophosphamide (50 mg PO BID x
7d q 14d), and celecoxib (400 mg PO BID). Serologic responses to a variety of recombinant
CTAs as well as delayed type hypersensitivity to autologous epigenetically modified tumor
cells will be assessed before and after vaccination.
-To assess the safety of an epigenetically modified autologous tumor cell vaccine
administered with ISCOMATRIX(Trademark) adjuvant in combination with metronomic oral
cyclophosphamide and celecoxib in patients undergoing thoracic metastasectomy.
- To ascertain if autologous epigenetically modified tumor cell vaccines induce immunity
to CTAs in patients following thoracic metastasectomy
- To compare CT-X gene expression profiles in established autologous parental tumor cells
relative to epigenetically modified cell lines
- To examine if oral metronomic cyclophosphamide and celecoxib therapy diminishes the
number and percentage of T regulatory cells in patients with resected thoracic
metastases who are at risk of recurrence
- Patients with histologically or cytologically proven sarcoma, melanoma, or epithelial
malignancies metastatic to lungs, pleura or mediastinum who can be rendered no evidence
of disease (NED) by metastasectomy.
- Patients must be 18 years or older with an ECOG performance status of 0 - 2, without
evidence of unstable or decompensated myocardial disease. Patients must have adequate
pulmonary reserve evidenced by FEV1 and DLCO equal to or greater than 30% predicted;
pCO2 less than 50 mm Hg and pO2 greater than 60 mm Hg on room air ABG; and be on no
immunosuppressive medications except inhaled corticosteroids at the time vaccination
- Patients must have a platelet count greater than 100,000, an ANC equal to or greater
than 1500 without transfusion or cytokine support, a normal PT, and adequate hepatic
function as evidenced by a total bilirubin of < 1.5 x upper limits of normal. Serum
creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater
than 70 ml/min/1.73m(2) at the time vaccination commences.
- Patients will undergo thoracic metastasectomy using standard of practice guidelines.
- Portions of the resected tumors will be transferred to the Thoracic Oncology
Laboratory. 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 metronomic oral cyclophosphamide and
- 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
- 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
- Approximately 80 patients will be accrued to this trial in order to obtain up to 20
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To assess the safety of an epigenetically modified autologous tumor cell vaccine administered with ISCOMATRIX(Trademark) adjuvant in combination with metronomic oral cyclophosphamide and celecoxib in patients undergoing thoracic metastasectomy.
David S Schrump, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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