Tumor Cell Vaccine for Patients Undergoing Surgery for Sarcomas, Melanomas, Germ Cell Tumors, or Malignancies That Have Metastasized to the Lungs, Pleura, or Mediastinum
|ClinicalTrials.gov Identifier: NCT01313429|
Recruitment Status : Completed
First Posted : March 11, 2011
Last Update Posted : May 24, 2018
- Certain types of cancers, including sarcoma and melanoma, have specific antigens (protein molecules) on their surfaces. Research has shown that producing an immune reaction to these antigens may be able to keep tumors from growing by encouraging the immune system to destroy the tumor cells. By creating a vaccine that contains antigens similar to those found on the cancer cells, researchers hope to cause an immune reaction that targets the cancer cells. However, more research is needed to determine the safety and effectiveness of this type of vaccine treatment.
- To determine whether a tumor cell vaccine, given to individuals who have had surgery to remove malignant tumors from the chest, can cause an immune reaction that will prevent the tumors from coming back.
- Individuals at least 18 years of age who have been diagnosed with cancer that has spread to the lungs, pleura, or mediastinum, and have recently had surgery to remove tumors in the chest.
- Participants will be screened with a physical examination and medical history, as well as blood tests and imaging studies.
- Participants will have the option to have leukapheresis to collect white blood cells for studies on how the body is responding to the vaccine. Participants who agree to have this procedure will have it before the start of treatment and after the sixth and eighth vaccines.
- Seven days before the first vaccine, participants will receive the chemotherapy drugs celecoxib and cyclophosphamide to take twice a day at home.
- Participants will receive the experimental vaccine as an injection in the thigh or arm, and may receive it in two shots depending on how many cells are in each vaccine. Participants will receive a diary to monitor medication doses and side effects, as well as additional cyclophosphamide and celecoxib to take at home as directed by the study.
- Participants will have one vaccine every month for 6 months, and will have regular blood tests and imaging studies. After the sixth vaccine, participants who have successfully responded to the treatment will have two additional vaccines given 3 months apart.
- After the eighth vaccine, participants will have followup visits every 3 months for 1 year and then every 6 months for up to 4 years.
|Condition or disease||Intervention/treatment||Phase|
|Sarcoma Melanoma Epithelial Malignancies Pleural Malignancies||Drug: Cyclophosphamide Biological: Allogenic tumor Cell Vaccine (K562) Drug: Celecoxib||Phase 1|
During recent years, the cancer-testis (CT) antigens (CTA) have emerged as attractive targets for cancer immunotherapy. Whereas malignancies of diverse histologies express a variety of CTAs, immune responses to these antigens appear uncommon in cancer patients, possibly due to low-level, heterogeneous antigen expression, as well as immunosuppressive regulatory T cells. Conceivably, vaccination of cancer patients with allogeneic tumor cells expressing high levels of multiple CTAs in combination with depletion of T regulatory cells will induce broad immunity to these antigens. In order to examine this issue, patients with sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to lungs, pleura or mediastinum will be vaccinated with irradiated K562 erythroleukemia cells expressing GM-CSF (K562-GM) following thoracic metastasectomy. Vaccines will be administered in conjunction with 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 will be assessed before and after vaccination.
-To assess the safety of K562-GM allogeneic tumor cell vaccines in combination with oral metronomic cyclophosphamide and celecoxib in patients undergoing thoracic metastasectomy.
- Patients with histologically or cytologically proven sarcoma, melanoma, or epithelial malignancies metastatic to lungs, pleura or mediastinum who can be rendered no clinical evidence of active disease (NED).
- 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 commences.
- 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 times 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.
- Following recovery from thoracic metastasectomy, patients with NED or MRD will be vaccinated via deep subcutaneous injection with 1x10(8) irradiated K562 GM-tumor cells periodically over 6 months.
- Vaccines will be administered in conjunction with metronomic oral cyclophosphamide and celecoxib.
- Systemic toxicities, and immunologic response to therapy will be recorded. Pre and post vaccination serologic responses to a standard panel of CT antigens as well as cell mediated responses to epigenetically-modified autologous EBV-transformed B and autologous tumor cells (if available) 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.
- 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 25 patients will be accrued to this trial.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Adjuvant Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Sarcomas, Melanomas, Germ Cell Tumors, or Epithelial Malignancies Metastatic to Lungs, Pleura, or Mediastinum|
|Study Start Date :||March 10, 2011|
|Actual Primary Completion Date :||June 20, 2014|
|Actual Study Completion Date :||June 20, 2014|
tumor cell vaccine administered with chemotherapy
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.
Biological: Allogenic tumor Cell Vaccine (K562)
4 vaccines consisting of approximately 2.5E7 cells each will be delivered IM every 4 weeks for 6 months. If immune response is detected after first 6 vaccinations, 2 more may be given at 3 month intervals.
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.
- Summary of adverse events [ Time Frame: 30 days after last vaccine (up to 13 months) ]List of adverse event frequency
- Number and description of immunologic responses to a panel of CT antigens in vaccinated patients [ Time Frame: After last vaccine ]Number and description of immunologic responses to a panel of CT antigens in vaccinated patients
- Paired t test analysis of difference between number and percentage of T reg cells at baseline and at treatment conclusion [ Time Frame: After last vaccine ]Assessment of T regs in peripheral blood before and after initiation of CP/celecoxib treatment
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01313429
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||David S Schrump, M.D.||National Cancer Institute (NCI)|