Adjuvant Tumor Lysate Vaccine and Iscomatrix With or Without Metronomic Oral Cyclophosphamide and Celecoxib in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum
During recent years, cancer-testis (CT) antigens (CTA), particularly those encoded by genes on the X chromosome (CT-X genes), have emerged as attractive targets for cancer immunotherapy. Whereas malignancies of diverse histologies express a variety of CTAs, immune responses to these proteins appear uncommon in cancer patients, possibly due to low-level, heterogeneous antigen expression, as well as immunosuppressive regulatory T cells present within tumor sites and systemic circulation of these individuals. Conceivably, vaccination of cancer patients with tumor cells expressing high levels of CTAs in combination with regimens that deplete or inhibit T regulatory cells will induce broad immunity to these antigens. In order to examine this issue, patients with primary lung and esophageal cancers, pleural mesotheliomas, thoracic sarcomas, thymic neoplasms and mediastinal germ cell tumors, as well as sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to lungs, pleura or mediastinum with no evidence of disease (NED) or minimal residual disease (MRD) following standard multidisciplinary therapy will be vaccinated with H1299 tumor cell lysates with Iscomatrix adjuvant. Vaccines will be administered with or without 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 immunologic responses to autologous tumor or epigenetically modified autologous EBVtransformed lymphocytes will be assessed before and after a six month vaccination period.
1. To assess the frequency of immunologic responses to CTAs in patients with thoracic malignancies following vaccinations with H1299 cell lysate/Iscomatrix(TM) vaccines alone in comparison to patients with thoracic malignancies following vaccinations with H1299 cell lysate/Iscomatrix vaccines in combination with metronomic cyclophosphamide and celecoxib.
- To examine if oral metronomic cyclophosphamide and celecoxib therapy diminishes the number and percentage of T regulatory cells and diminishes activity of these cells in patients with thoracic malignancies are at risk of recurrence.
- To examine if H1299 cell lysate/Iscomatrix(TM) vaccination enhances immunologic response to autologous tumor or epigenetically modified autologous EBV-transformed lymphocytes (B cells).
- Patients with histologically or cytologically proven small cell or non-small cell lung cancer (SCLC;NSCLC), esophageal cancer (EsC), malignant pleural mesothelioma (MPM) , thymic or mediastinal germ cell tumors, thoracic sarcomas, or melanomas, sarcomas, or epithelial malignancies metastatic to lungs, pleura or mediastinum who have no clinical evidence of active disease (NED), or minimal residual disease (MRD) not readily accessible by non-invasive biopsy or resection/radiation following standard therapy completed within the past 26 weeks.
- Patients must be 18 years or older with an ECOG performance status of 0 2.
- Patients must have adequate bone marrow, kidney, liver, lung and cardiac function.
- Patients may not be on systemic immunosuppressive medications at time vaccinations commence
- Following recovery from surgery, chemotherapy, or chemo/XRT, patients with NED or MRD will be vaccinated via IM injection with H1299 cell lysates and Iscomatrix(TM) adjuvant monthly for 6 months.
- Vaccines will be administered with or without with metronomic oral cyclophosphamide and celecoxib.
- Systemic toxicities and immunologic response to therapy will be recorded. Pre and post vaccination serologic and cell mediated responses to a standard panel of CT antigens as well as autologous tumor cells (if available) and EBV-transformed lymphocytes will be assessed before and after vaccination.
- Numbers/percentages and function of T regulatory cells in peripheral blood will be assessed before, during, and after vaccinations.
- Patients will be followed in the clinic with routine staging scans until disease recurrence.
- The trial will randomize 28 evaluable patients per arm to either receive vaccine alone or vaccine plus chemotherapy in order to have 80% power to determine if the frequency of immune responses on the combination arm exceeds that of the vaccine alone arm, if the expected frequencies of immune responses on the two arms were 20% and 50%, using a one-sided 0.10 alpha level Fisher s exact test.
- Approximately 60 patients will be accrued to this trial.
Malignant Pleural Mesothelioma
Biological: H1299 Lysate Vaccine
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Adjuvant Tumor Lysate Vaccine and Iscomatrix With or Without Metronomic Oral Cyclophosphamide and Celecoxib in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum|
- Comparison of immune response rates in patients taking vaccine alone versus those taking vaccine plus metronomic chemotherapy. [ Time Frame: 6-12 months ] [ Designated as safety issue: No ]
- Immune response rate in patients taking vaccine alone [ Time Frame: 6-12 months ] [ Designated as safety issue: No ]
- Immune response rate in pateitns taking vaccine plus metronomic chemotherapy. [ Time Frame: 6-12 months ] [ Designated as safety issue: No ]
|Study Start Date:||January 2014|
|Estimated Study Completion Date:||November 2017|
|Estimated Primary Completion Date:||November 2017 (Final data collection date for primary outcome measure)|
|Experimental: Vaccine with metronomic chemotherapy||
Biological: H1299 Lysate Vaccine
1x10^8 H1299 cells administered in 2 IM injections q cycle. (1 cycle = 28 days) for 6 cycles if no toxicity and then up to an additional 6 cycles if immune response is evident after the first 6 cycles.Drug: Cyclophosphamide
50 mg PO BID for 7 days prior to the first dose of vaccine and then on days 8 through 14, and 22 through 28 of each treatment cycle for 6 cycles if no toxicity and then up to an additional 6 cycles if immune response is evident after the first 6 cycles.Drug: Celecoxib
400 mg PO BID for 7 days prior to the first dose of vaccine and then on days 1 through 28 of each vaccine cycle for 6 cycles if no toxicity and then up to an additional 6 cycles if immune response is evident after the first 6 cycles.
|Active Comparator: Vaccine alone||
Biological: H1299 Lysate Vaccine
1x10^8 H1299 cells administered in 2 IM injections q cycle. (1 cycle = 28 days) for 6 cycles if no toxicity and then up to an additional 6 cycles if immune response is evident after the first 6 cycles.
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT02054104
|Contact: Tricia Kunst, R.N.||(301) firstname.lastname@example.org|
|Contact: David S Schrump, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center 866-820-4505 firstname.lastname@example.org|
|Principal Investigator:||David S Schrump, M.D.||National Cancer Institute (NCI)|